Non-acute effects of different doses of 3, 4-methylenedioxymethamphetamine on spatial memory in the Morris water maze in Sprague-Dawley male rats

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

Dissociation between Performances in Water Maze and Spontaneous Alternation in BALB/C versus A/J Mice

Learning processes are extensively studied in behavioral neuroscience. As experimental models, Morris Water Maze (MWM) and Spontaneous Alternation (SA) represent two of the most frequently used laboratory tests to respectively address spatial vs non-spatial tasks. Several factors have been shown to impact on those learning, including strain, gender, apparatus, conditioning, vision, lighting conditions and stress level. In order to focus on the later, we compared the acquisition of two learning tasks (MWM and SA) in BALB/c and A/J mice, which are known as fearful and stress-sensitive strains. Here, we report that BALB/c mice exhibited higher performances than A/J mice in the MWM (i.e. spatial reference memory task), whereas A/J mice performed better in the SA (i.e. spatial working memory task). These results indicate dissociated processes in the acquisition of spatial vs non-spatial tasks, and emphasize a varying influence of emotional reactivity on different forms of cognition.

Hyperbaric oxygen therapy improves cognitive functioning after brain injury

Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hy- perbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney＇s free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats＇ spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was sig- nificantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly im- proves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is me- diated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.

Therapeutic potential of Gastrodia elata Blume for the treatment of Alzheimer's disease

Several studies have demonstrated that the Chinese herb Gastrodia elata Blume can protect against amyloid beta-peptide （Ap）-induced cell death. To investigate the possible therapeutic effects of Gastrodia elata Blume on Alzheimer＇s disease, we established a rat model of AIzheimer＇s disease by injecting A325-35 into bilateral hippocampi. These rats were intragastrically administered 500 or 1 000 mg/kg Gastrodia elata Blume per day for 52 consecutive days. Morris water maze tests showed that Gastrodia elata Blume treatment significantly improved the spatial memory of Alzheimer＇s disease rats. Congo red staining revealed that Gastrodia elata Blume significantly reduced the number of amyloid deposits in the hippocampus of these rats. Western blot analysis showed that choline acetyltransferase expression in the medial septum and hippocampus was significantly increased by the treatment of Gastrodia elata Blume, while EIIman method showed significant decrease in the activity of acetylcholinesterase in all three regions （prefrontal cortex, medial septum and hippocampus）. These findings suggest that long-term administration of Gastrodia elata Blume has therapeutic potential for Alzheimer＇s disease.

L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway

As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.

Acupuncture improves dendritic structure and spatial learning and memory ability of Alzheimer's disease mice

Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on improving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai（CV6）, Zhongwan（CV12）, Danzhong（CV17）, bilateral Zusanli（ST36）, and bilateral Xuehai（SP10） acupoints was performed once a day（1-day rest after 6-day treatment） for 14 consecutive days. Senescence-accelerated mouse prone 8（SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1（SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.Acupuncture can improve the cognitive state of Alzheimer＇s disease, but its mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer＇s disease brain are positively correlated with cognitive damage. Therefore, we speculated that the effect of acupuncture on im- proving cognitive function may be associated with reduced dendritic damage in the brain. Acupuncture at Qihai （CV6）, Zhongwan （CV 12）, Danzhong （CV17）, bilateral Zusanli （ST36）, and bilateral Xuehai （SP10） acupoints was performed once a day （1-day rest after 6-day treat- ment） for 14 consecutive days. Senescence-accelerated mouse prone 8 （SAMP8） mice without acupuncture and senescence-accelerated mouse resistant 1 （SAMR1） mice were used as normal controls. After 14 days of treatment, spatial learning and memory ability of mice was assessed in each group using the Morris water maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were analyzed by quantitative Golgi staining. Our results showed that acupuncture shortened escape latency and lengthened retention time of the former platform quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in the number of apical and basal dendritic branches and total length of apical and basal dendrites after acupuncture. These results suggest that acupuncture improves spatial learning and memory ability of middle-aged SAMP8 mice by ameliorating dendritic structure.

An enriched environment increases the expression of fibronectin type Ⅲ domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain

Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.

Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy

Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cog- nitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.

Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation

Glucagon-like peptide-1 receptor has anti-apoptotic,anti-inflammatory,and neuroprotective effects.It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses;however,it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms.We explored the effects of glucagon-like peptide-1 receptor on nociception,cognition,and neuroinflammation in chronic pain.A rat model of chronic pain was established using left L5 spinal nerve ligation.The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation.Electrophysiological examinations showed that,after treatment with exendin-4,paw withdrawal frequency of the left limb was significantly reduced,and pain was relieved.In addition,in the Morris water maze test,escape latency increased and the time to reach the platform decreased following exendin-4 treatment.Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus,as well as an increase in the expression of tumor necrosis factor alpha,interleukin 1 beta,and interleukin 6.All of these effects could be reversed by exendin-4 treatment.These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China(approval No.WDRM 20171214)on September 22,2017.

Chrysophanol attenuates lead exposure-induced injury to hippocampal neurons in neonatal mice

Previous studies have shown that chrysophanol protects against learning and memory impairments in lead-exposed adult mice. In the present study, we investigated whether chrysophanol can alleviate learning and memory dysfunction and hippocampal neuronal injury in lead-exposed neonatal mice. At the end of lactation, chrysophanol（0.1, 1.0, 10.0 mg/kg） was administered to the neonatal mice by intraperitoneal injection for 15 days. Chrysophanol significantly alleviated injury to hippocampal neurons and improved learning and memory abilities in the lead-poisoned neonatal mice. Chrysophanol also significantly decreased lead content in blood, brain, heart, spleen, liver and kidney in the lead-exposed neonatal mice. The levels of malondialdehyde in the brain, liver and kidney were significantly reduced, and superoxide dismutase and glutathione peroxidase activities were significantly increased after chrysophanol treatment. Collectively, these findings indicate that chrysophanol can significantly reduce damage to hippocampal neurons in lead-exposed neonatal mice.

Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

BACKGROUND： Modem pharmacological studies have demonstrated that Panax notoginseng saponins （PNS） can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer＇s disease （AD） remains unclear. OBJECTIVE： Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A. DESIGN： A completely randomized grouping design, controlled animal experiment. SETTING： Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University. MATERIALS： Ninety healthy Wistar rats of both genders, 15-month-old （n =75） and 3-month-old rats as young controls （n =15）, were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd （permission No. Z53021485, Yuxi, Yunan Province, China）. Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science. METHODS： This study was performed at the Center of Research ＆ Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each： model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose （5 mL/kg） every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μ L ibotenic acid （5 g/L） bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension （0.3 mg/kg） was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES： After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency （time-to-platform）, number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS： Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test： Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups （both P 〈 0.05）. No significant differences in these two indices were measured among the administration groups （all P 〉 0.05）. Results of spatial probe test： Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups （P 〈 0.05）. There were no significant differences in these two indices among the administration groups （P 〉 0.05）. CONCLUSION： PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.

Association between Alzheimer's disease pathogenesis and early demyelination and oligodendrocyte dysfunction

The APPSwe/PSEN1 dE9（APP/PS1） transgenic mouse model is an Alzheimer＇s disease mouse model exhibiting symptoms of dementia, and is commonly used to explore pathological changes in the development of Alzheimer＇s disease. Previous clinical autopsy and imaging studies suggest that Alzheimer＇s disease patients have white matter and oligodendrocyte damage, but the underlying mechanisms of these have not been revealed. Therefore, the present study used APP/PS1 mice to assess cognitive change, myelin loss, and corresponding changes in oligodendrocytes, and to explore the underlying mechanisms. Morris water maze tests were performed to evaluate cognitive change in APP/PS1 mice and normal C57 BL/6 mice aged 3 and 6 months. Luxol fast blue staining of the corpus callosum and quantitative reverse transcription-polymerase chain reaction（q RT-PCR） for myelin basic protein（MBP） mRNA were carried out to quantify myelin damage. Immunohistochemistry staining for NG2 and qRT-PCR for monocarboxylic acid transporter 1（MCT1） mRNA were conducted to assess corresponding changes in oligodendrocytes. Our results demonstrate that compared with C57 BL/6 mice, there was a downregulation of MBP mRNA in APP/PS1 mice aged 3 months. This became more obvious in APP/PS1 mice aged 6 months accompanied by other abnormalities such as prolonged escape latency in the Morris water maze test, shrinkage of the corpus callosum, upregulation of NG2-immunoreactive cells, and downregulation of MCT1 mRNA. These findings indicate that the involvement of early demyelination at 3 months and the oligodendrocyte dysfunction at 6 months in APP/PS1 mice are in association with Alzheimer＇s disease pathogenesis.

Collagen/heparan sulfate porous scaffolds loaded with neural stem cells improve neurological function in a rat model of traumatic brain injury

One reason for the poor therapeutic effects of stem cell transplantation in traumatic brain injury is that exogenous neural stem cells cannot effectively migrate to the local injury site,resulting in poor adhesion and proliferation of neural stem cells at the injured area.To enhance the targeted delivery of exogenous stem cells to the injury site,cell therapy combined with neural tissue engineering technology is expected to become a new strategy for treating traumatic brain injury.Collagen/heparan sulfate porous scaffolds,prepared using a freeze-drying method,have stable physical and chemical properties.These scaffolds also have good cell biocompatibility because of their high porosity,which is suitable for the proliferation and migration of neural stem cells.In the present study,collagen/heparan sulfate porous scaffolds loaded with neural stem cells were used to treat a rat model of traumatic brain injury,which was established using the controlled cortical impact method.At 2 months after the implantation of collagen/heparan sulfate porous scaffolds loaded with neural stem cells,there was significantly improved regeneration of neurons,nerve fibers,synapses,and myelin sheaths in the injured brain tissue.Furthermore,brain edema and cell apoptosis were significantly reduced,and rat motor and cognitive functions were markedly recovered.These findings suggest that the novel collagen/heparan sulfate porous scaffold loaded with neural stem cells can improve neurological function in a rat model of traumatic brain injury.This study was approved by the Institutional Ethics Committee of Characteristic Medical Center of Chinese People’s Armed Police Force,China(approval No.2017-0007.2)on February 10,2019.

DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

Objective To examine the effect of docosahexaenoic acid （DHA） deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain, DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze （MWM） was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain, The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Condusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

Progressive paradoxical sleep deprivation impairs partial memory following learning tasks in rats

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.

Enriched environment upregulates growth-associated protein 43 expression in the hippocampus and enhances cognitive abilities in prenatally stressed rat offspring

In our previous study, we reported that prenatal restraint stress could induce cognitive deficits, which correlated with a change in expression of growth-associated protein 43 in the hippocampus. In this study, we investigated the effects of enriched environment on cognitive abilities in prenatally stressed rat offspring, as well as the underlying mechanisms. Reverse transcription-PCR and western blot assay results revealed that growth-associated protein 43 mRNA and protein levels were upregulated on postnatal day 15 in the prenatal restraint stress group. Growth-associated protein 43 expression was significantly lower in the prenatal restraint stress group compared with the negative control and prenatal restraint stress plus enriched environment groups on postnatal days 30 and 50. Morris water maze test demonstrated that cognitive abilities were noticeably increased in rats from the prenatal restraint stress plus enriched environment group on postnatal day 50. These results indicate that enriched environment can improve the spatial learning and memory ability of prenatally stressed offspring by upregulating growth-associated protein 43 expression.

Target inhibition of caspase-8 alleviates brain damage after subarachnoid hemorrhage

Caspase-8 plays an important role in the mediation of inflammation and the effect of its role in subarachnoid hemorrhage remains elusive.The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome has been postulated to mediate inflammation during SAH.The aim of the present study was to investigate the effects of caspase-8 inhibition on SAH injury and further elucidate the molecular mechanisms.In this study,a subarachnoid hemorrhage model was established by endovascular perforation process in adult male Sprague-Dawley rats.Z-IETD-FMK(0.5,1,2 mg/kg;an inhibitor of caspase-8)was delivered via intravenous(tail vein)injection immediately after subarachnoid hemorrhage.After 12 hours of subarachnoid hemorrhage,western blot assay showed that the expression of cleaved caspase-8 was significantly increased at 12 hours,peaked at 24 hours,and then decreased at 72 hours after subarachnoid hemorrhage.Immunofluorescence staining demonstrated that caspase-8 was expressed in microglia after subarachnoid hemorrhage.Z-IETDFMK significantly improved neurological deficits and reduced brain water content 24 hours after subarachnoid hemorrhage.The Morris water maze and rotarod test confirmed that Z-IETD-FMK significantly improved spatial learning and memory abilities and motor coordination at 21–27 days after subarachnoid hemorrhage.Furthermore,inhibition of caspase-8 activation reduced the expression of pyrin domain-containing 3,caspase-1,and interleukin-1βafter subarachnoid hemorrhage.In conclusion,our findings suggest that caspase-8 inhibition alleviates subarachnoid hemorrhage-induced brain injuries by suppressing inflammation.The study was approved by the Institutional Animal Ethics Committee of the First Affiliated Hospital,School of Medicine,Zhejiang University,China(approval No.2016-193)on February 25,2016.

Endogenous adult neurogenesis and cognitive function recovery following traumatic brain injury in the rat hippocampus

BACKGROUND：Endogenous neural progenitor cells play a beneficial role for cognitive recovery following traumatic brain injury.However,there are few classification-control studies aimed at varying graded brain trauma.OBJECTIVE：To observe the effects of adult endogenous neurogenesis on cognitive function repair and regeneration of neural progenitor cells following varying graded traumatic hippocampal injury to determine the significance of endogenous neurogenesis in the repair of brain injury.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at the Key Laboratory of Injuries,Variations and Regeneration of Nervous System,Tianjin Medical University General Hospital,from February to October 2009.MATERIALS：Mouse anti-rat 5-bromodeoxyuridine （BrdU） and neuronal nuclei （NeuN） monoclonal antibodies were purchased from Millipore Corporation,USA.METHODS：A total of 45 Wistar rats were randomly assigned to three groups.Mild and severe injury groups were respectively subjected to （182 ± 2） kPa and （284 ± 4） kPa lateral fluid percussion to establish models of brain injury,and the control group was subjected to surgery with no lateral fluid percussion.MAIN OUTCOME MEASURES：Cognitive function was estimated using the Morris water maze.Proliferation,survival,and differentiation of newly generated cells in the injured hippocampus were observed through the use of immunofluorescent staining.RESULTS：At 7 days post-injury,the number of BrdU＋ cells in the hippocampal dentate gyrus significantly increased in the mild and severe injury groups compared with the control group （P〈0.01）.At 61 days post-injury,the number of BrdU7NeuN＋ cells in the hippocampal dentate gyrus was significantly greater in the mild injury group compared with the severe injury and control groups （P〈 0.01）.In addition,the control group exhibited the greatest proportion of surviving cells that differentiated into mature neurons compared with the injury groups （P〈 0.01）.Moreover,at 61 days post-injury,cognitive function in rats with mild injury recovered to normal levels,whereas the severe injury group exhibited cognitive deficits （P〈 0.01）.CONCLUSION：Traumatic brain injury may be a stimulation factor for proliferation of neural progenitor cells in the adult hippocampus but severe brain trauma does not lead to an increased number of newly generated cells.Endogenous adult neurogenesis repairs neurological functions to an extent.However,recovery of neurological function remains limited following severe traumatic brain injury.

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

An experimental model of schizophrenia was established using dizocilpine （MK-801）. Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets

Objective:To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase(TK)expression and activity.Methods:To test this,we separated 50 rats into five groups that were either fed a standard chow diet(controls)or a high-fat diet(experimental groups HO,HI,H2,and H3).HO group animals received no additional dietary supplementation,while H1 group animals were administered 100 mg/kg body weight(BW)thiamine,100 mg/kg BW riboflavin,and 250 mg/kg BW niacin each day,and group H2 animals received daily doses of 100 mg/kg BW pyridoxine,100 mg/kg BW cobalamin,and 5 mg/kg BW folate.Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day.Results:Over time,group HO exhibited greater increases in BW and fat mass relative to other groups.When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion(CTA)and Morris Water Maze(MWM),we found B vitamin treatment was associated with significant improvements relative to untreated HO controls.Similarly,B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in HO(P<0.05).Conclusion:Together,these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity.As such,B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.