In order to study the relationship between landmarks and spatial memory in short-nosed fruit bat, Cynopterus sphinx (Megachiroptera, Pteropodidae), we simulated a foraging environment in the laboratory. Different la...In order to study the relationship between landmarks and spatial memory in short-nosed fruit bat, Cynopterus sphinx (Megachiroptera, Pteropodidae), we simulated a foraging environment in the laboratory. Different landmarks were placed to gauge the spatial memory of C. sphinx. We changed the number of landmarks every day with 0 landmarks again on the fifth day (from 0, 2, 4, 8 to 0). Individuals from the control group were exposed to the identical artificial foraging environment, but without landmarks. The results indicated that there was significant correlation between the time of the first foraging and the experimental days in both groups (Pearson Correlation: experimental group: r=-0.593, P〈0.01; control group: r=-0.581, P〈0.01). There was no significant correlation between the success rates of foraging and the experimental days in experimental groups (Pearson Correlation: r=0.177, P〉0.05), but there was significant correlation between the success rates of foraging and the experimental days in the control groups (Pearson Correlation: r=0.445, P〈0.05). There was no significant difference for the first foraging time between experimental and control groups (GLM: F0.05,1=4.703, P〉0.05); also, there was no significant difference in success rates of foraging between these two groups (GLM: F0.05,1=0.849,P〉0.05). The results of our experiment suggest that spatial memory in C. sphinx was formed gradually and that the placed landmarks appeared to have no discernable effects on the memory of the foraging space.展开更多
Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on f...Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on func- tional improvement in AD. In this study, we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone. We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model, the senescence-accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks. Our results showed that, when provided separately, memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant. When combined, memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone. Consistent with the behavior results, pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP) levels. Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice, indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD.展开更多
3, 4-methylenedioxymethamphetamine (MDMA; also known as 'ecstasy') has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory....3, 4-methylenedioxymethamphetamine (MDMA; also known as 'ecstasy') has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory. In the present study, we intraperitoneally administered MDMA (0, 5, 10, 20 mg/kg) to adult male rats to investigate the effects of different doses on rat spatial memory in the Morris water maze, body temperature, and mortality, twice a day, for 7 successive days. The results indicated that MDMA impaired spatial memory dose-dependently, with the highest dose (20 mg/kg) exerting the strongest effects. In addition, MDMA also caused hyperthermia and increased mortality in rats展开更多
Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in trea...Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO) II mRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COII mRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.展开更多
Autonomous navigation for intelligent mobile robots has gained significant attention,with a focus on enabling robots to generate reliable policies based on maintenance of spatial memory.In this paper,we propose a lear...Autonomous navigation for intelligent mobile robots has gained significant attention,with a focus on enabling robots to generate reliable policies based on maintenance of spatial memory.In this paper,we propose a learning-based visual navigation pipeline that uses topological maps as memory configurations.We introduce a unique online topology construction approach that fuses odometry pose estimation and perceptual similarity estimation.This tackles the issues of topological node redundancy and incorrect edge connections,which stem from the distribution gap between the spatial and perceptual domains.Furthermore,we propose a differentiable graph extraction structure,the topology multi-factor transformer(TMFT).This structure utilizes graph neural networks to integrate global memory and incorporates a multi-factor attention mechanism to underscore elements closely related to relevant target cues for policy generation.Results from photorealistic simulations on image-goal navigation tasks highlight the superior navigation performance of our proposed pipeline compared to existing memory structures.Comprehensive validation through behavior visualization,interpretability tests,and real-world deployment further underscore the adapt-ability and efficacy of our method.展开更多
The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shre...The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shrew (Tupaia belangen chinensis) were reported in present paper. The results read as follows: In the DR performance with training, the rhesus monkeys and slow lorises could reach a criterion of 90% correct response at 1.1 ± 3.2 seconds, and 3.8±0.4 seconds delay interval, respectively, by 1000 training trails. The tree shrews failed to reach the criterion of 90% correct response even at 0 seconds delay interval by 1000 training trails. If a delay interval was tested in one session (30 trails) only, doing the DR performamce without training, the rhesus monkeys reached a correct of 80% or higher in each session at 0, 1, 2, 3, 4, and 5 seconds delay, respectively. The percent correct in each session of the slow lorises showed no differences from the rhesus monkeys at 0, 1, 2, 3, and 4 seconds delay. However, when the delay interval was increased to 5 seconds, the percent correct of the DR performance declined to 70% or lower in the slow lorises. In the tree shrews the percent correct in each session reached to 70% or lower at 0, 1, 2, 3, 4, and 5 seconds delay interval, respectively. The morphological studies revealed that the size of the prefrontal cortex increased, and the structure got complex in the course of the evolution in primates. It is suggested that the relation of evolution between the spatial working memory function and anatomy in the prefrontal cortex might be significant among the three species, both the development of morphology and that of the spatial working memory function in the dorsolateral prefrontal cortex are later than other regions of cerebral cortex in phylogenetic evolution course.展开更多
In Alzheimer抯 disease (AD), hyperphosphorylation of tau may be the underlying mechanism for the cytoskeletal abnormalities and neuronal death. It was reported that cy-clin-dependent kinase5 (cdk-5) could phosphorylat...In Alzheimer抯 disease (AD), hyperphosphorylation of tau may be the underlying mechanism for the cytoskeletal abnormalities and neuronal death. It was reported that cy-clin-dependent kinase5 (cdk-5) could phosphorylate tau at most AD-related epitopes in vitro. In this study, we investigated the effect of cdk-5 overexpression on tau phosphorylation and spatial memory in rat. We demonstrated that 24 h after transfection into rat hippocampus, cdk-5 was overexpressed and induced a reduced staining with antibody tau-1 and an enhanced staining with antibodies 12e8 and PHF-1, suggesting hyperphosphorylation of tau at Ser199/202, Ser262/356 and Ser396/404 sites. Additionally, the cdk-5 transfected rats showed long latency to find the hidden platform in Morris water maze compared to the control rat. 48 h after transfection, the level of cdk-5 was decreased significantly, and the latency of rats to find the hidden platform was prolonged. It implies that in vivo overexpression of cdk-5 leads to impairment of spatial memory in rat and tau hyperphosphorylation may be the underlying mechanism.展开更多
Background Human amniotic epithelial cells (HAECs), which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In t...Background Human amniotic epithelial cells (HAECs), which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer's disease (AD) coexpressing presenilin-1 (PS1) and mutant Sweden amyloid precursor protein (APPswe) genes. Methods The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly divided into two groups respectively: the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. was used to track the survival of HAECs. Immunohistochemistry was used octamer-binding protein 4 (Oct-4) and Nanog in the HAECs. High performance measure acetylcholine in hippocampus. The density of cholinergic neurons in hippocampus was measured using acetylcholinesterase staining. Immunofluorescence cytochemistry to determine the expression of quid chromatography was used to basal forebrain and nerve fibers in Results Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites. Conclusions These results demonstrate that intracerebroventricular transplantation of HAECs can improve the spatial memory of the double TG mice. The higher content of acetylcholine in hippocampus released by more survived cholinergic neurites is one of the causes of this improvement.展开更多
The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we gen...The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.展开更多
Background As the widespread use of electric devices in modern life, human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever. Over the past decades, a substantial number ...Background As the widespread use of electric devices in modern life, human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever. Over the past decades, a substantial number of epidemiological and experimental studies have demonstrated that ELF MF (50 Hz) exposure is associated with increased risk of various health effects. The present study examined the effects of chronic exposure to ELF MF on anxiety level and spatial memory of adult rats. Methods The 50-Hz ELF MF was used during the whole experimental procedures and the value of magnetic field (MF) was set to 2 mT. Adult rats were divided randomly to control, MF 1 hour and MF 4 hours group. Anxiety-related behaviors were examined in the open field test and the elevated plus maze; changes in spatial learning and memory were determined in Morris water maze aRer 4 weeks of daily exposure. Results Rats in MF 4 hours group had increased anxiety-like behaviors with unaltered locomotor activity. In the Morris water maze test, rats had reduced latency to find the hidden platform and improved long-term memory of former location of platform without changes in short-term memory and locomotor activity. Conclusion Chronic ELF MF exposure has anxiogenic effect on rats, and the promoting effects on spatial learning and long-term retention of spatial memory.展开更多
Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia.Hypoxemia is a common complication during perianesthesia.We want to know the effect of propofol on spatial memory and ...Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia.Hypoxemia is a common complication during perianesthesia.We want to know the effect of propofol on spatial memory and LTP(Long-term potentiation)under hypoxic conditions.In this study,84 seven-day-old SpragueeDawley rats were randomly assigned into six groups(n Z 14)-four control groups:lipid emulsion solvent t 50%oxygen(CO),lipid emulsion solvent t room air(CA),lipid emulsion solvent t 18%oxygen(CH),and propofol t 50%oxygen(propofoleoxygen,PO);and two experiment groups:propofol t room air(propofol eair,PA),and propofol t 18%oxygen(propofolehypoxia,PH).After receiving propofol(50 mg/kg)or the same volume of intralipid intraperitoneal(5.0 ml/kg),injected once per day for seven consecutive days,the rats were exposed to 18%oxygen,50%oxygen and air,until recovery of the righting reflex.We found that the apoptotic index and activated caspase-3 increased in the PH group(P<0.05)compared with the PA group,fEPSP(field excitatory postsynaptic)potential and success induction rate of LTP reduced in all propofol groups(P<0.05).Compared with the PO group,the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups(P<0.05).Moreover,compared with CH group,the average time of escape latency was longer,and the number of platform location crossings was significantly reduced in the PH group(P<0.05).Thus,we believe that adequate oxygen is very important during propofol anesthesia.展开更多
Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role i...Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.展开更多
Objective It has been shown that there are extensive interactions between the central nervous system and the immune system.The present study focused on the effects of lipopolysaccharide(LPS)on memory retrieval,to ex...Objective It has been shown that there are extensive interactions between the central nervous system and the immune system.The present study focused on the effects of lipopolysaccharide(LPS)on memory retrieval,to explore the interaction between immune activation and memory.Methods C57BL/6J mice(8 weeks old)were first trained in the Morris water maze to reach asymptotic performance.Then mice were tested 24 h after the last training session and LPS was administered(1.25 mg/kg,i.p.)4 h prior to the testing.The retrieval of spatial memory was tested by probe trial,and the time spent in the target quadrant and the number of platform location crosses were recorded.ELISA was performed to detect interleukin-1β(IL-1β)protein level in the hippocampus of mice tested in the water maze.Results Although LPS induced overt sickness behavior and a significant increase in the level of IL-1β in the hippocampus of mice,there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing.Conclusion Immune activation induced by LPS does not impair the retrieval of spatial memory.展开更多
Although it has been suggested that olfaction is closely interconnected with hippocampal systems,whether olfaction regulates spatial memory strategy remains never known.Furthermore,no study has examined how olfaction ...Although it has been suggested that olfaction is closely interconnected with hippocampal systems,whether olfaction regulates spatial memory strategy remains never known.Furthermore,no study has examined how olfaction mediates spatial memory established on the external objects,for example,caches made by scatter-hoarding animals.Here,we experimentally induced nondestructive and reversible olfaction loss of a scatter-hoarding animal Leopoldamys edwardsi,to test whether and how olfaction regulates spatial memory to mediate cache recovery and pilferage.Our results showed that the normal L.edwardsi preferred to pilfer caches of others rather than to recover their own using accurate spatial memory(35.7%vs.18.6%).Anosmic L.edwardsi preferred to recover the caches they made prior to olfaction loss rather than to pilfer from others relied on spatial memory(54.2%vs.36.0%).However,L.edwardsi with anosmia showed no preference either to the caches they established after olfaction loss or caches made by others(25.8%vs.29.1%).These collectively indicate that olfaction loss has a potential to affect new memory formation but not previously established spatial memory on caches.Our study first showed that olfaction modified spatial memory strategy in cache recovery and pilferage behaviors of scatter-hoarding animals.We suggest that future studies pay more attention to the evolution of olfaction and its relationship with spatial memory strategy.展开更多
BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects o...BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled tria SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University. MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). METHODS : The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES : The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.50 ±3.80), (31.38_±3.72), (61.60±3.61) s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11 ±1 ), (10±1), (8_±1), (8±1), (4±1) times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups (P 〉 0.05). CONCLUSION : TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.展开更多
BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them ...BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.展开更多
Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its appl...Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.展开更多
With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstr...With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.展开更多
BACKGROUND: Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by "flower pot" technique, on spatial refere...BACKGROUND: Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by "flower pot" technique, on spatial reference memory and working memory require further research. OBJECTIVE: To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING: Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS: Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS: All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the "flower pot" technique for 72 hours, housing the rats on small platforms over water. Rats in the "tank control" and "home cage control" groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES: Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Maze. RESULTS: Twenty-eight rats were included in the final analysis, without any loss. In the first trial, between day 2 and 4, escape latency and swimming distance increased significantly in the paradoxical sleep deprivation group compared to the home cage control and tank control groups (P 〈 0.01); percentage of time in correct quarter and memory scores, however, decreased in the paradoxical sleep deprivation group compared to the home cage control and tank control groups (P 〈 0.01). The escape latency, swimming distance, percentage of time in correct quarter, and memory scores in the second trial was not significantly different among the three groups (P 〉 0.05). CONCLUSION: Paradoxical sleep deprivation inhibits spatial reference memory, but not working memory.展开更多
BACKGROUND: Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertai...BACKGROUND: Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertain whether the intellectual activities required to play Go are related to the frontal lobe. OBJECTIVE: To investigate various patterns of brain region activity while schizophrenic patients and normal subjects engaged in memorizing piece placement in the Chinese game of Go. Spatial working memory was measured in order to validate whether the prefrontal lobe participates in this memory process. DESIGN, TIME AND SETTING: Non-randomized, concurrent control trial was performed at Second Xiangya Hospital of Central South University, between May and December 2004. PARTICIPANTS: A total of nine Chinese schizophrenic patients with no brain or bodily diseases and not undergoing electroshock treatment, who were in accordance with the DSM-Ⅳ criteria for schizophrenia, as well as thirteen healthy staffs and students with matched age, sex, and education were included. Patients and control subjects had no neurological disorders or mental retardation. In addition, all participants were right-handed. METHODS: The cognitive task for functional magnetic resonance imaging was a block design experiment. Both groups were asked to remember the placement of pieces in the Chinese game of Go on a computer screen. A brain activation map was analyzed in SPM99. MAIN OUTCOME MEASURES: Brain responses were compared with regard to activation region size, volume, and asymmetry indices. RESULTS: Compared with the control group, the reaction time was significantly delayed in schizophrenics performing the working memory task (P 〈 0.05). When performing the tasks, normal subjects showed significant activation of the bilateral dorsolateral prefrontal lobe with left dominance; the asymmetry indices were: frontal lobe, +0.32; temporal lobe, 0.58; parietal lobe, 0.41 ; and occipital lobe, 0.34. On the other hand, schizophrenics showed right dominance and had a broader activation region of the prefrontal lobe (asymmetry indices: frontal lobe, 0.10; temporal lobe, +0.38; parietal lobe, +0.24; and occipital lobe, 0.00). When comparing the normal group subtracted with the schizophrenic group, no significant lateralization was found in the frontal lobes but significant activation was found in the left anterior central gyrus, left middle frontal gyrus and in both sides of the cingulate gyrus. Comparing the schizophrenic group subtracted with the normal group, there was significant right lateralization of the frontal lobe and abnormally activated regions on both sides of the anterior central gyrus, middle frontal gyrus, left inferior frontal gyrus, right medial frontal gyrus and the right insular lobe. CONCLUSION: Different brain activation regions are involved in memorizing the placement of pieces in Chinese Go between schizophrenia and healthy subjects. Schizophrenics showed right dominance and border activation range, indicating that the prefrontal cortex plays an important role in memory information processing and resource allocation when remembering piece placement in the game of Go.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,No30800102)Natural Science Foundation of Hainan Province(309026)
文摘In order to study the relationship between landmarks and spatial memory in short-nosed fruit bat, Cynopterus sphinx (Megachiroptera, Pteropodidae), we simulated a foraging environment in the laboratory. Different landmarks were placed to gauge the spatial memory of C. sphinx. We changed the number of landmarks every day with 0 landmarks again on the fifth day (from 0, 2, 4, 8 to 0). Individuals from the control group were exposed to the identical artificial foraging environment, but without landmarks. The results indicated that there was significant correlation between the time of the first foraging and the experimental days in both groups (Pearson Correlation: experimental group: r=-0.593, P〈0.01; control group: r=-0.581, P〈0.01). There was no significant correlation between the success rates of foraging and the experimental days in experimental groups (Pearson Correlation: r=0.177, P〉0.05), but there was significant correlation between the success rates of foraging and the experimental days in the control groups (Pearson Correlation: r=0.445, P〈0.05). There was no significant difference for the first foraging time between experimental and control groups (GLM: F0.05,1=4.703, P〉0.05); also, there was no significant difference in success rates of foraging between these two groups (GLM: F0.05,1=0.849,P〉0.05). The results of our experiment suggest that spatial memory in C. sphinx was formed gradually and that the placed landmarks appeared to have no discernable effects on the memory of the foraging space.
基金supported by a grant from the Natural Sciences Foundation of Jiangsu Province (No. BK2008081)the Scientific Research Fund of Nanjing Medical University (No. 2010NJMU244)
文摘Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on func- tional improvement in AD. In this study, we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone. We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model, the senescence-accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks. Our results showed that, when provided separately, memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant. When combined, memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone. Consistent with the behavior results, pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP) levels. Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice, indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD.
基金a grant from the Substance Abuse and Dependence Research Center University of Social Welfare and Rehabilitation Sciences, No. 313-126417Tehran University of Medical Sciences, No. P/664
文摘3, 4-methylenedioxymethamphetamine (MDMA; also known as 'ecstasy') has been shown to impair learning and spatial memory in adult and neonatal rats. Many studies have focused on the acute effects of MDMA on memory. In the present study, we intraperitoneally administered MDMA (0, 5, 10, 20 mg/kg) to adult male rats to investigate the effects of different doses on rat spatial memory in the Morris water maze, body temperature, and mortality, twice a day, for 7 successive days. The results indicated that MDMA impaired spatial memory dose-dependently, with the highest dose (20 mg/kg) exerting the strongest effects. In addition, MDMA also caused hyperthermia and increased mortality in rats
基金This program was supported by National Natural Science Foundation of China (No. 39830450)
文摘Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO) II mRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COII mRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.
基金supported in part by the National Natural Science Foundation of China (62225309,62073222,U21A20480,62361166632)。
文摘Autonomous navigation for intelligent mobile robots has gained significant attention,with a focus on enabling robots to generate reliable policies based on maintenance of spatial memory.In this paper,we propose a learning-based visual navigation pipeline that uses topological maps as memory configurations.We introduce a unique online topology construction approach that fuses odometry pose estimation and perceptual similarity estimation.This tackles the issues of topological node redundancy and incorrect edge connections,which stem from the distribution gap between the spatial and perceptual domains.Furthermore,we propose a differentiable graph extraction structure,the topology multi-factor transformer(TMFT).This structure utilizes graph neural networks to integrate global memory and incorporates a multi-factor attention mechanism to underscore elements closely related to relevant target cues for policy generation.Results from photorealistic simulations on image-goal navigation tasks highlight the superior navigation performance of our proposed pipeline compared to existing memory structures.Comprehensive validation through behavior visualization,interpretability tests,and real-world deployment further underscore the adapt-ability and efficacy of our method.
文摘The relation between evolution of spatial working memory function and of morphology of the dorsolateral prefrontal cortex among the rhesus monkey (Macaca mulatta), the slow loris (Nycticebus coucang) and the tree shrew (Tupaia belangen chinensis) were reported in present paper. The results read as follows: In the DR performance with training, the rhesus monkeys and slow lorises could reach a criterion of 90% correct response at 1.1 ± 3.2 seconds, and 3.8±0.4 seconds delay interval, respectively, by 1000 training trails. The tree shrews failed to reach the criterion of 90% correct response even at 0 seconds delay interval by 1000 training trails. If a delay interval was tested in one session (30 trails) only, doing the DR performamce without training, the rhesus monkeys reached a correct of 80% or higher in each session at 0, 1, 2, 3, 4, and 5 seconds delay, respectively. The percent correct in each session of the slow lorises showed no differences from the rhesus monkeys at 0, 1, 2, 3, and 4 seconds delay. However, when the delay interval was increased to 5 seconds, the percent correct of the DR performance declined to 70% or lower in the slow lorises. In the tree shrews the percent correct in each session reached to 70% or lower at 0, 1, 2, 3, 4, and 5 seconds delay interval, respectively. The morphological studies revealed that the size of the prefrontal cortex increased, and the structure got complex in the course of the evolution in primates. It is suggested that the relation of evolution between the spatial working memory function and anatomy in the prefrontal cortex might be significant among the three species, both the development of morphology and that of the spatial working memory function in the dorsolateral prefrontal cortex are later than other regions of cerebral cortex in phylogenetic evolution course.
基金This work was supported in part by the National Natural Science Foundation of China(Grant Nos.39925012,30100057&30170221)Science and Technology Committee of China(G1999054007)National Educational Committee of China(2001-171).
文摘In Alzheimer抯 disease (AD), hyperphosphorylation of tau may be the underlying mechanism for the cytoskeletal abnormalities and neuronal death. It was reported that cy-clin-dependent kinase5 (cdk-5) could phosphorylate tau at most AD-related epitopes in vitro. In this study, we investigated the effect of cdk-5 overexpression on tau phosphorylation and spatial memory in rat. We demonstrated that 24 h after transfection into rat hippocampus, cdk-5 was overexpressed and induced a reduced staining with antibody tau-1 and an enhanced staining with antibodies 12e8 and PHF-1, suggesting hyperphosphorylation of tau at Ser199/202, Ser262/356 and Ser396/404 sites. Additionally, the cdk-5 transfected rats showed long latency to find the hidden platform in Morris water maze compared to the control rat. 48 h after transfection, the level of cdk-5 was decreased significantly, and the latency of rats to find the hidden platform was prolonged. It implies that in vivo overexpression of cdk-5 leads to impairment of spatial memory in rat and tau hyperphosphorylation may be the underlying mechanism.
基金The project was supported by grants from the National Natural Science Foundation of China (No. 30271325) and the Major State Basic Resarch Development Program of China ("973" Program) (No. 2005CB522604).
文摘Background Human amniotic epithelial cells (HAECs), which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer's disease (AD) coexpressing presenilin-1 (PS1) and mutant Sweden amyloid precursor protein (APPswe) genes. Methods The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly divided into two groups respectively: the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. was used to track the survival of HAECs. Immunohistochemistry was used octamer-binding protein 4 (Oct-4) and Nanog in the HAECs. High performance measure acetylcholine in hippocampus. The density of cholinergic neurons in hippocampus was measured using acetylcholinesterase staining. Immunofluorescence cytochemistry to determine the expression of quid chromatography was used to basal forebrain and nerve fibers in Results Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites. Conclusions These results demonstrate that intracerebroventricular transplantation of HAECs can improve the spatial memory of the double TG mice. The higher content of acetylcholine in hippocampus released by more survived cholinergic neurites is one of the causes of this improvement.
基金supported by the National Natural Science Foundation of China (31721002, 81920208014, 31930051, 81800133)China Postdoctoral Science Foundation Funded Project (2018M642853)。
文摘The raphe nucleus is critical for feeding, rewarding and memory. However, how the heterogenous raphe neurons are molecularly and structurally organized to engage their divergent functions remains unknown. Here, we genetically target a subset of neurons expressing VGLUT3. VGLUT3 neurons control the efficacy of spatial memory retrieval by synapsing directly with parvalbumin-expressing GABA interneurons(PGIs) in the dentate gyrus. In a mouse model of Alzheimer's disease(AD mice),VGLUT3→PGIs synaptic transmission is impaired by ETV4 inhibition of VGLUT3 transcription. ETV4 binds to a promoter region of VGLUT3 and activates VGLUT3 transcription in VGLUT3 neurons. Strengthening VGLUT3→PGIs synaptic transmission by ETV4 activation of VGLUT3 transcription upscales the efficacy of spatial memory retrieval in AD mice. This study reports a novel circuit and molecular mechanism underlying the efficacy of spatial memory retrieval via ETV4 inhibition of VGLUT3 transcription and hence provides a promising target for therapeutic intervention of the disease progression.
文摘Background As the widespread use of electric devices in modern life, human are exposed to extremely low frequency magnetic fields (ELF MF) much more frequently than ever. Over the past decades, a substantial number of epidemiological and experimental studies have demonstrated that ELF MF (50 Hz) exposure is associated with increased risk of various health effects. The present study examined the effects of chronic exposure to ELF MF on anxiety level and spatial memory of adult rats. Methods The 50-Hz ELF MF was used during the whole experimental procedures and the value of magnetic field (MF) was set to 2 mT. Adult rats were divided randomly to control, MF 1 hour and MF 4 hours group. Anxiety-related behaviors were examined in the open field test and the elevated plus maze; changes in spatial learning and memory were determined in Morris water maze aRer 4 weeks of daily exposure. Results Rats in MF 4 hours group had increased anxiety-like behaviors with unaltered locomotor activity. In the Morris water maze test, rats had reduced latency to find the hidden platform and improved long-term memory of former location of platform without changes in short-term memory and locomotor activity. Conclusion Chronic ELF MF exposure has anxiogenic effect on rats, and the promoting effects on spatial learning and long-term retention of spatial memory.
基金This study was supported by the National Natural Science Foundation of China[31200853]Health Commission of Chongqing,China[2015HBRC007]+1 种基金Natural Science Foundation of Chongqing[cstc2012jjA10036]National Key Clinical Program([2013]544).
文摘Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia.Hypoxemia is a common complication during perianesthesia.We want to know the effect of propofol on spatial memory and LTP(Long-term potentiation)under hypoxic conditions.In this study,84 seven-day-old SpragueeDawley rats were randomly assigned into six groups(n Z 14)-four control groups:lipid emulsion solvent t 50%oxygen(CO),lipid emulsion solvent t room air(CA),lipid emulsion solvent t 18%oxygen(CH),and propofol t 50%oxygen(propofoleoxygen,PO);and two experiment groups:propofol t room air(propofol eair,PA),and propofol t 18%oxygen(propofolehypoxia,PH).After receiving propofol(50 mg/kg)or the same volume of intralipid intraperitoneal(5.0 ml/kg),injected once per day for seven consecutive days,the rats were exposed to 18%oxygen,50%oxygen and air,until recovery of the righting reflex.We found that the apoptotic index and activated caspase-3 increased in the PH group(P<0.05)compared with the PA group,fEPSP(field excitatory postsynaptic)potential and success induction rate of LTP reduced in all propofol groups(P<0.05).Compared with the PO group,the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups(P<0.05).Moreover,compared with CH group,the average time of escape latency was longer,and the number of platform location crossings was significantly reduced in the PH group(P<0.05).Thus,we believe that adequate oxygen is very important during propofol anesthesia.
基金supported by the National Natural Science Foundation of China,No.82101567Doctoral Start-up Foundation of Liaoning Province,No.2021-BS-111345 Talent Project of Shengjing Hospital of China Medical University,No.M0673(all to XYF)。
文摘Cerebral ischemia/reperfusion injury impairs learning and memory in patients.Studies have shown that synaptic function is involved in the formation and development of memory,and that DNA methylation plays a key role in the regulation of learning and memory.To investigate the role of DNA hypomethylation in cerebral ischemia/reperfusion injury,in this study,we established a rat model of cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery and then treated the rats with intraperitoneal 5-aza-2′-deoxycytidine,an inhibitor of DNA methylation.Our results showed that 5-aza-2′-deoxycytidine markedly improved the neurological function,and cognitive,social and spatial memory abilities,and dose-dependently increased the synaptic density and the expression of SYP and SHANK2 proteins in the hippocampus in a dose-dependent manner in rats with cerebral ischemia/reperfusion injury.The effects of 5-aza-2′-deoxycytidine were closely related to its reduction of genomic DNA methylation and DNA methylation at specific sites of the Syp and Shank2 genes in rats with cerebral ischemia/reperfusion injury.These findings suggest that inhibition of DNA methylation by 5-aza-2′-deoxycytidine promotes the recovery of learning and memory impairment in a rat model of cerebral ischemia/reperfusion injury.These results provide theoretical evidence for stroke treatment using epigenetic methods.
基金supported by the National Natural Science Foundation of China(No.30700213)National Basic Research Development Program of China(No.2007CB947804)
文摘Objective It has been shown that there are extensive interactions between the central nervous system and the immune system.The present study focused on the effects of lipopolysaccharide(LPS)on memory retrieval,to explore the interaction between immune activation and memory.Methods C57BL/6J mice(8 weeks old)were first trained in the Morris water maze to reach asymptotic performance.Then mice were tested 24 h after the last training session and LPS was administered(1.25 mg/kg,i.p.)4 h prior to the testing.The retrieval of spatial memory was tested by probe trial,and the time spent in the target quadrant and the number of platform location crosses were recorded.ELISA was performed to detect interleukin-1β(IL-1β)protein level in the hippocampus of mice tested in the water maze.Results Although LPS induced overt sickness behavior and a significant increase in the level of IL-1β in the hippocampus of mice,there was no significant difference in the time spent in the target quadrant or in the number of platform location crosses between LPS-treated and control groups in the probe trial testing.Conclusion Immune activation induced by LPS does not impair the retrieval of spatial memory.
基金provided by the National Natural Science Foundation of China(32070447,31760156)the Young Talents Invitation Program of Shandong Provincial Colleges and Universities(20190601)。
文摘Although it has been suggested that olfaction is closely interconnected with hippocampal systems,whether olfaction regulates spatial memory strategy remains never known.Furthermore,no study has examined how olfaction mediates spatial memory established on the external objects,for example,caches made by scatter-hoarding animals.Here,we experimentally induced nondestructive and reversible olfaction loss of a scatter-hoarding animal Leopoldamys edwardsi,to test whether and how olfaction regulates spatial memory to mediate cache recovery and pilferage.Our results showed that the normal L.edwardsi preferred to pilfer caches of others rather than to recover their own using accurate spatial memory(35.7%vs.18.6%).Anosmic L.edwardsi preferred to recover the caches they made prior to olfaction loss rather than to pilfer from others relied on spatial memory(54.2%vs.36.0%).However,L.edwardsi with anosmia showed no preference either to the caches they established after olfaction loss or caches made by others(25.8%vs.29.1%).These collectively indicate that olfaction loss has a potential to affect new memory formation but not previously established spatial memory on caches.Our study first showed that olfaction modified spatial memory strategy in cache recovery and pilferage behaviors of scatter-hoarding animals.We suggest that future studies pay more attention to the evolution of olfaction and its relationship with spatial memory strategy.
基金the National Natural Science Foundation of China, No. 30170300 30300109
文摘BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled tria SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University. MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd (Lot Number: 2004051106, Specification: 2 mL/piece). METHODS : The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES : The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS: Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [(23.92±2.21), (41.84±3.74), (39.50 ±3.80), (31.38_±3.72), (61.60±3.61) s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [(36.27±3.42) %, (35.84±2.54)%, (38.43±3.08)%, (36.51±1.96)%, (22.24±3.46)%; (11 ±1 ), (10±1), (8_±1), (8±1), (4±1) times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral (left) parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [(98±8), (65±5), (53±6), (57±6), (37±6)/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups (P 〉 0.05). CONCLUSION : TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.
文摘BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied. OBJECTIVE: To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion. DESIGN: Randomized controlled animal study. SETTING: Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University. MATERIALS: A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA), and NGF (1× 106 U/L, 0.5 mL, Siweite Company, Dalian). METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to July 2005. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham-operation group were separated of the vessels without occlusion or administration. The neural function was evaluated with Zea Longa 5-grade scale. Animals with the score of one, two and three points received Morris water-maze test to measure searching time on platform (omitting platform-escaping latency). Meanwhile, leaning and memory abilities of animals were reflected through testing times of passing through platform per minute. MAIN OUTCOME MEASURES: Experimental results of omitting platform-escaping latency and spatial probe. RESULTS: Three and two rats in the ischemia/reperfusion group and treatment group respectively were not in accordance with the criteria in the process, and the rest were involved in the final analysis. ① Comparisons of platform-escaping latency during Morris water-maze test in all the three groups: Ten days after modeling, the platform-escaping latency in the ischemia/reperfusion group was obviously longer than that in sham-operation group (P < 0.01), and was significantly shorter than that in the treatment group (P < 0.01). ② Comparisons of times of passing through platform in all the three groups: Times of passing through platform were remarkably less in the ischemia/reperfusion group than those in the sham-operation group [(1.79±0.39), (4.30±0.73) times/minute, P < 0.01], and those were markedly more in the treatment group than the ischemia/reperfusion group [(3.16±1.03), (1.79±0.39) times/minute, P < 0.01]. CONCLUSION: CGRP and NGF are capable of ameliorating the abilities of spatial learning and memory in MCAO rats, which indicates that CGRP and NGF can protect ischemic neurons.
基金supported by STI2030-Major Projects,No.2022ZD0207600 (to LZ)the National Natural Science Foundation of China,Nos.821 71446 (to JY),U22A20301 (to KFS),32070955 (to LZ)+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.202381515040015 (to LZ)Science and Technology Program of Guangzhou of China,No.202007030012 (to KFS and LZ)
文摘Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.
文摘With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.
基金the National Natural Science Foundation of China, No.30670677
文摘BACKGROUND: Complex learning tasks result in a greater number of paradoxical sleep phases, which can improve memory. The effect of paradoxical sleep deprivation, induced by "flower pot" technique, on spatial reference memory and working memory require further research. OBJECTIVE: To observe the effect of progressive paradoxical sleep deprivation in rats, subsequent to learning, on memory using the Morris Water Maze. DESIGN, TIME AND SETTING: Controlled observation experiment. The experiment was performed at the Laboratory of Neurobiology, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Lanzhou University from December 2006 to October 2007. MATERIALS: Twenty-eight, male, Wistar rats, 3-4 months old, were provided by the Experimental Animal Center of Lanzhou University. The Morris Water Maze and behavioral analyses system was purchased from Genheart Company, Beijing, China. METHODS: All animals, according to a random digits table, were randomly divided into paradoxical sleep deprivation, tank control, and home cage control groups. Paradoxical sleep deprivation was induced by the "flower pot" technique for 72 hours, housing the rats on small platforms over water. Rats in the "tank control" and "home cage control" groups were housed either in a tank with large platforms over the water or in normal cages without paradoxical sleep deprivation. MAIN OUTCOME MEASURES: Morris Water Maze was employed for task learning and spatial memory testing. Rats in all groups were placed at six random starting points each day for four consecutive days. Each placement was repeated for two trials; the first trial represented reference memory and the second working memory. Rats in the first trial were allowed to locate the submerged platform within 120 seconds. Data, including swimming distance, escape latency, swimming velocity, percentage of time in correct quarter, and memory scores were recorded and analyzed automatically by behavioral analyses systems for Morris Water Maze. RESULTS: Twenty-eight rats were included in the final analysis, without any loss. In the first trial, between day 2 and 4, escape latency and swimming distance increased significantly in the paradoxical sleep deprivation group compared to the home cage control and tank control groups (P 〈 0.01); percentage of time in correct quarter and memory scores, however, decreased in the paradoxical sleep deprivation group compared to the home cage control and tank control groups (P 〈 0.01). The escape latency, swimming distance, percentage of time in correct quarter, and memory scores in the second trial was not significantly different among the three groups (P 〉 0.05). CONCLUSION: Paradoxical sleep deprivation inhibits spatial reference memory, but not working memory.
基金Supported by:the National Science Foundation for Distinguished Young Scholars,No.60225015the National Natural Science Foundation of China, No.30100054,30570609
文摘BACKGROUND: Go, a traditional Chinese chess-like game, requires many unknown functions of the brain including attention, imaging, problem solving and processing of spatial working memory. To date, it remains uncertain whether the intellectual activities required to play Go are related to the frontal lobe. OBJECTIVE: To investigate various patterns of brain region activity while schizophrenic patients and normal subjects engaged in memorizing piece placement in the Chinese game of Go. Spatial working memory was measured in order to validate whether the prefrontal lobe participates in this memory process. DESIGN, TIME AND SETTING: Non-randomized, concurrent control trial was performed at Second Xiangya Hospital of Central South University, between May and December 2004. PARTICIPANTS: A total of nine Chinese schizophrenic patients with no brain or bodily diseases and not undergoing electroshock treatment, who were in accordance with the DSM-Ⅳ criteria for schizophrenia, as well as thirteen healthy staffs and students with matched age, sex, and education were included. Patients and control subjects had no neurological disorders or mental retardation. In addition, all participants were right-handed. METHODS: The cognitive task for functional magnetic resonance imaging was a block design experiment. Both groups were asked to remember the placement of pieces in the Chinese game of Go on a computer screen. A brain activation map was analyzed in SPM99. MAIN OUTCOME MEASURES: Brain responses were compared with regard to activation region size, volume, and asymmetry indices. RESULTS: Compared with the control group, the reaction time was significantly delayed in schizophrenics performing the working memory task (P 〈 0.05). When performing the tasks, normal subjects showed significant activation of the bilateral dorsolateral prefrontal lobe with left dominance; the asymmetry indices were: frontal lobe, +0.32; temporal lobe, 0.58; parietal lobe, 0.41 ; and occipital lobe, 0.34. On the other hand, schizophrenics showed right dominance and had a broader activation region of the prefrontal lobe (asymmetry indices: frontal lobe, 0.10; temporal lobe, +0.38; parietal lobe, +0.24; and occipital lobe, 0.00). When comparing the normal group subtracted with the schizophrenic group, no significant lateralization was found in the frontal lobes but significant activation was found in the left anterior central gyrus, left middle frontal gyrus and in both sides of the cingulate gyrus. Comparing the schizophrenic group subtracted with the normal group, there was significant right lateralization of the frontal lobe and abnormally activated regions on both sides of the anterior central gyrus, middle frontal gyrus, left inferior frontal gyrus, right medial frontal gyrus and the right insular lobe. CONCLUSION: Different brain activation regions are involved in memorizing the placement of pieces in Chinese Go between schizophrenia and healthy subjects. Schizophrenics showed right dominance and border activation range, indicating that the prefrontal cortex plays an important role in memory information processing and resource allocation when remembering piece placement in the game of Go.