Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.

Astrocytic endothelin-1 overexpression impairs learning and memory ability in ischemic stroke via altered hippocampal neurogenesis and lipid metabolism

Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

Tree shrew models:A chronic social defeat model of depression and a one-trial captive conditioning model of learning and memory

Recent genome studies indicate that tree shrew is in the order or a closest sister of primates,and thus may be one of the best animals to model human diseases.In this paper,we report on a social defeat model of depression in tree shrew（Tupaia belangeri chinensis）.Two male tree shrews were housed in a pair-cage consisting of two independent cages separated by a wire mesh partition with a door connecting the two cages.After one week adaptation,the connecting door was opened and a brief fighting occurs between the two male tree shrews and this social conflict session consisted of 1 h direct conflict（fighting） and 23 h indirect influence（e.g.smell,visual cues） per day for 21 days.The defeated tree shrew was considered the subordinate.Compared with na？ve animals,subordinate tree shrews at the final week of social conflict session showed alterations in body weight,locomotion,avoidance behavior and urinary cortisol levels.Remarkably,these alterations persisted for over two weeks.We also report on a novel captive conditioning model of learning and memory in tree shrew.An automatic trapping cage was placed in a small closed room with a freely-moving tree shrew.For the first four trials,the tree shrew was not trapped when it entered the cage and ate the bait apple,but it was trapped and kept in the cage for 1 h on the fifth trial.Latency was defined as the time between release of the tree shrew and when it entered the captive cage.Latencies during the five trials indicated adaptation.A test trial 24 h later was used to measure whether the one-trial trapping during the fifth trial could form captive memory.Tree shrews showed much longer trapping latencies in the test trial than the adaptation trials.The N-methyl-d-aspartate（NMDA） receptor antagonist MK-801（0.2 mg/kg,i.p.）,known to prevent the formation of memory,did not affect latencies in the adaptation trails,but did block captive memory as it led to much shorter trapping latencies compared to saline treatment in the test trial.These results demonstrate a chronic social defeat model of depression and a novel one-trial captive conditioning model for learning and memory in tree shrews,which are important for mechanism studies of depression,learning,memory,and preclinical evaluation for new antidepressants.

Machine learning-assisted efficient design of Cu-based shape memory alloy with specific phase transition temperature

The martensitic transformation temperature is the basis for the application of shape memory alloys(SMAs),and the ability to quickly and accurately predict the transformation temperature of SMAs has very important practical significance.In this work,machine learning(ML)methods were utilized to accelerate the search for shape memory alloys with targeted properties(phase transition temperature).A group of component data was selected to design shape memory alloys using reverse design method from numerous unexplored data.Component modeling and feature modeling were used to predict the phase transition temperature of the shape memory alloys.The experimental results of the shape memory alloys were obtained to verify the effectiveness of the support vector regression(SVR)model.The results show that the machine learning model can obtain target materials more efficiently and pertinently,and realize the accurate and rapid design of shape memory alloys with specific target phase transition temperature.On this basis,the relationship between phase transition temperature and material descriptors is analyzed,and it is proved that the key factors affecting the phase transition temperature of shape memory alloys are based on the strength of the bond energy between atoms.This work provides new ideas for the controllable design and performance optimization of Cu-based shape memory alloys.

Fabrication and integration of photonic devices for phase-change memory and neuromorphic computing

In the past decade,there has been tremendous progress in integrating chalcogenide phase-change materials(PCMs)on the silicon photonic platform for non-volatile memory to neuromorphic in-memory computing applications.In particular,these non von Neumann computational elements and systems benefit from mass manufacturing of silicon photonic integrated circuits(PICs)on 8-inch wafers using a 130 nm complementary metal-oxide semiconductor line.Chip manufacturing based on deep-ultraviolet lithography and electron-beam lithography enables rapid prototyping of PICs,which can be integrated with high-quality PCMs based on the wafer-scale sputtering technique as a back-end-of-line process.In this article,we present an overview of recent advances in waveguide integrated PCM memory cells,functional devices,and neuromorphic systems,with an emphasis on fabrication and integration processes to attain state-of-the-art device performance.After a short overview of PCM based photonic devices,we discuss the materials properties of the functional layer as well as the progress on the light guiding layer,namely,the silicon and germanium waveguide platforms.Next,we discuss the cleanroom fabrication flow of waveguide devices integrated with thin films and nanowires,silicon waveguides and plasmonic microheaters for the electrothermal switching of PCMs and mixed-mode operation.Finally,the fabrication of photonic and photonic–electronic neuromorphic computing systems is reviewed.These systems consist of arrays of PCM memory elements for associative learning,matrix-vector multiplication,and pattern recognition.With large-scale integration,the neuromorphic photonic computing paradigm holds the promise to outperform digital electronic accelerators by taking the advantages of ultra-high bandwidth,high speed,and energy-efficient operation in running machine learning algorithms.

DeepBio:A Deep CNN and Bi-LSTM Learning for Person Identification Using Ear Biometrics

The identification of individuals through ear images is a prominent area of study in the biometric sector.Facial recognition systems have faced challenges during the COVID-19 pandemic due to mask-wearing,prompting the exploration of supplementary biometric measures such as ear biometrics.The research proposes a Deep Learning(DL)framework,termed DeepBio,using ear biometrics for human identification.It employs two DL models and five datasets,including IIT Delhi(IITD-I and IITD-II),annotated web images(AWI),mathematical analysis of images(AMI),and EARVN1.Data augmentation techniques such as flipping,translation,and Gaussian noise are applied to enhance model performance and mitigate overfitting.Feature extraction and human identification are conducted using a hybrid approach combining Convolutional Neural Networks(CNN)and Bidirectional Long Short-Term Memory(Bi-LSTM).The DeepBio framework achieves high recognition rates of 97.97%,99.37%,98.57%,94.5%,and 96.87%on the respective datasets.Comparative analysis with existing techniques demonstrates improvements of 0.41%,0.47%,12%,and 9.75%on IITD-II,AMI,AWE,and EARVN1 datasets,respectively.

Effects of GBE50 on hippocampal CA1 synaptic plasticity,learning and memory in an experimental rat model of aging

The content of total flavonoids in an extract of Ginkgo biloba, called GBE50, is 44% by weight. This is significantly greater than that in a standard extract of Ginkgo biloba, designated EGB761. To date, the mechanisms by which GBE50 and EGB761 function remain poorly understood. In the present study, an experimental rat model of aging was induced by intraperitoneal injection of D-galactose, followed by intragastric perfusion of GBE50 （30, 60 mg/kg）, or EGB761 （60 mg/kg）. The water maze scores and hippocampal CA1 synaptic plasticity were evaluated. In the place navigation test, the GBE50 group rats did better than EGB761, while similar scores were obtained in the spatial probe test, and in the platform-switched test. In addition, long-term potentiation was significantly enhanced following high-frequency stimulation in the GBE50 and EGB761 groups, compared with the model group. These results demonstrate that GBE50 and EGB761 improved the learning and memory of aging rats. In particular, GBE50 administered at the 60 mg/kg dose exhibited superior effects over EGB761 at the same 60 mg/kg dose. Furthermore, the enhancement of hippocampal synaptic plasticity may be an underlying mechanism.

Basic roles of key molecules connected with NMDAR signaling pathway on regulating learning and memory and synaptic plasticity

With key roles in essential brain functions ranging from the long-term potentiation(LTP) to synaptic plasticity,the N-methyl-D-aspartic acid receptor(NMDAR) can be considered as one of the fundamental glutamate receptors in the central nervous system.The role of NMDA R was first identified in synaptic plasticity and has been extensively studied.Some molecules,such as Ca^(2+),postsynaptic density 95(PSD-95),calcium/calmodulin-dependent protein kinase II(Ca MK II),protein kinase A(PKA),mitogen-activated protein kinase(MAPK) and cyclic adenosine monophosphate(c AMP) responsive element binding protein(CREB),are of special importance in learning and memory.This review mainly focused on the new research of key molecules connected with learning and memory,which played important roles in the NMDAR signaling pathway.

Possible mechanisms of lycopene amelioration of learning and memory impairment in rats with vascular dementia

Oxidative stress is involved in the pathogenesis of vascular dementia. Studies have shown that lycopene can significantly inhibit oxidative stress;therefore, we hypothesized that lycopene can reduce the level of oxidative stress in vascular dementia. A vascular dementia model was established by permanent bilateral ligation of common carotid arteries. The dosage groups were treated with lycopene(50, 100 and 200 mg/kg) every other day for 2 months. Rats without bilateral carotid artery ligation were prepared as a sham group. To test the ability of learning and memory, the Morris water maze was used to detect the average escape latency and the change of search strategy. Hematoxylin-eosin staining was used to observe changes of hippocampal neurons. The levels of oxidative stress factors, superoxide dismutase and malondialdehyde, were measured in the hippocampus by biochemical detection. The levels of reactive oxygen species in the hippocampus were observed by dihydroethidium staining. The distribution and expression of oxidative stress related protein, neuron-restrictive silencer factor, in hippocampal neurons were detected by immunofluorescence histochemistry and western blot assays. After 2 months of drug administration,(1) in the model group, the average escape latency was longer than that of the sham group, and the proportion of straight and tend tactics was lower than that of the sham group, and the hippocampal neurons were irregularly arranged and the cytoplasm was hyperchromatic.(2) The levels of reactive oxygen species and malondialdehyde in the hippocampus of the model group rats were increased, and the activity of superoxide dismutase was decreased.(3) Lycopene(50, 100 and 200 mg/kg) intervention improved the above changes, and the lycopene 100 mg/kg group showed the most significant improvement effect.(4) Neuron-restrictive silencer factor expression in the hippocampus was lower in the sham group and the lycopene 100 mg/kg group than in the model group.(5) The above data indicate that lycopene 100 mg/kg could protect against the learning-memory ability impairment of vascular dementia rats. The protective mechanism was achieved by inhibiting oxidative stress in the hippocampus. The experiment was approved by the Animal Ethics Committee of Fujian Medical University, China(approval No. 2014-025) in June 2014.

Effects of polygonatum sibiricum polysaccharide on learning and memory in a scopolamine-induced mouse model of dementia

BACKGROUND： Learning and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in learning and memory damage. OBJECTIVE： To observe the effects of polygonatum sibiricum polysaccharide （PSP） in comparison with vitamin 12 on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and learning and memory in a scopolamine-induced mouse model of dementia. DESIGN： Randomized controlled animal study. SETTINGS： Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd. MATERIALS： A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP （extracted and purified by Huangjing, Taishan） was provided by the Department of Traditional Chinese Medicine, Taishan Medical College （purity of 79.6% by using a phenol-concentrated sulphate acid method）, and hydrogen bromine acid scopolamine injection solution （SCO） by Shanghai Hefeng Pharmaceutical Co., Ltd. METHODS： This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. （1） A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin 12. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform （latent period） for 30 minutes, they were determined to have learned the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme （GSH-Px）, superoxide dismutase （SOD）, and the content of malondialdehyde （MDA） were assayed using an UV spectrophotometer. （2） The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded. MAIN OUTCOME MEASURE： （1） Numbers of error responses within 5 minutes on the platform. （2） GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. （3） Numbers and duration of mouth-opening breaths of the isolated mouse head. RESULTS： Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. （1） Effects of PSP on learning in mice： The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions （P 〈 0.05）. （2） Effects of PSP on memory in mice： The number of errors in the step-down test in the model group was higher than in the normal control group （P 〈 0.01）. Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups （P 〈 0.01）. （3） Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue： SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group （P 〉 0.05）. （4） Effects of PSP on acute cerebral ischemia in mice： The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head （P 〈 0.05, 0.01）. CONCLUSION： PSP can improve learning and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.

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.

Effect of Punica granatum peel extract on learning and memory in rats

Objective:To evaluate potential memory enhancing effect of Punica granatum peel extract on rats.Methods:Healthy adult male albino rats of Wistar strain were used.Each group of 6 rats were administered either distilled water or 50 mg/kg of extract or 100 mg/kg of extract for 15 days and subjected to passive avoidance test or T-maze test.In the next phase rats were administered distilled water or 100 mg/kg of extract for 15 days and the rats were given injection diazepam before subjecting them to the tests.Results:The overall performance was better in test groups compared to control groups.Among the test groups,100 mg/kg rats performed better than 50 mg/kg.The effect on spatial learning parameters like mean number of alternations and mean percentage bias was more marked compared to retention testing parameters like latency. 100 mg/kg Punica extract treated group also improved performance of diazepam treated rats. Conclusions:There is a definite trend of memory improvement by Punica granatum peel with effects being more marked on spatial learning tendency and long term memory than on retention capacity.

Synergistic effects of ginseng stem and leaf-extracted ginsenoside and choline on improving learning and memory in rats Association verification experiment in animals with multiple learning and memory disorders

BACKGROUND： Ginsenoside extracted from the stem and leaf of ginseng （GSL） and choline have both been shown to improve learning and memory functions; however, further studies are needed to understand the synergistic effects of a combination of both. OBJECTIVE： To verify the combined improved synergistic effects of GSL and choline on learning and memory disorders in rats. DESIGN： Control observation. SETTING： Taishan Medical College. MATERIALS： A total of 150 male Kunming mice weighing （204-2） g and 40 healthy male Wistar rats weighing （2204-20） g were provided by the Experimental Animal Department of Jilin University. Animal experimentation received confirmed consent from the local ethic committee. GSL was provided by the Department of Chemistry, Norman Bethune Medical University, and choline was provided by the Third Experiment Factory, Shanghai. METHODS： This study was performed at the Life Science Institute, Taishan Medical College from October 2006 to February 2007. ① Scopolamine-induced learning and memory disorders in rats： Forty rats were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋ 200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, 8 rats/group. Rats were perfused and administrated in the morning, once a day for 14 successive days. Rats in the control group and model group were perfused with 20 mL/kg distilled water and underwent Morris water maze spatial resolution test 1 hour after perfusion on the 10m, 11m, and 12m days after administration. Rats also underwent passive step-down avoidance test 1 hour after reperfusion on the 13m and 14m days after administration. Thirty minutes prior to experimentation, rats in the remaining three groups were intraperitoneally （i.p） injected with 2 mg/kg scopolamine, and rats in the control group were i.p. injected with 2 mL/kg saline. ② Scopolamine-induced learning disorder and memory acquired disorder in mice： Fifty mice were randomly divided into control group, model group, combination group （400 mg/kg GSL ＋200 mg/kg choline）, GSL （400 mg/kg） group, and choline （200 mg/kg） group, with 10 mice/group. Mice were perfused and administrated in the morning, once a day for 9 successive days. Mice in the control group and model group were perfused with 20 mL/kg distilled water and underwent passive step down avoidance test 1 hour after reperfusion on the 8th and 9th day after administration. Twenty minutes prior to training, mice in the remaining three groups were i.p. injected with 2 mg/kg scopolamine, and mice in the control group were i.p. injected with 10 mL/kg saline. ③ Sodium nitrite-induced memory consolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. After training, mice in the remaining three groups were immediately subcutaneously injected with 120 mg/kg sodium nitrite, and mice in the control group were subcutaneously injected with 20 mL/kg saline. ④ Ethanol-induced memory reconsolidation disorder in mice： Grouping, administration, and testing were the same as mentioned above. At 24 hours after training and 20 minutes before retraining, mice in the remaining four groups were perfused with 10 mL/kg ethanol （0.3 volume fraction）, and mice in the control group were perfused with 10 mL/kg saline. MAIN OUTCOME MEASURES： Synergistic effects of GSL and choline on learning and memory deficits induced by scopolamine, sodium nitrite, and ethanol in experimental animals. RESULTS： All 40 rats and 150 mice were included in the final analysis. ① Synergistic effects of GSL and choline on learning and memory disorders induced by scopolamine in rats： During passive step-down avoidance and Morris water maze spatial resolution tests, the number of error responses and length of maze training in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses and length of maze training in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests that the combination of GSL and choline had synergistic effects. ② Synergistic effects of GSL and choline on learning disorder and memory-acquired disorder induced by scopolamine in mice： During passive step-down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combining administration, which suggests GSL and choline had synergistic effects. ③ Synergistic effects of GSL and choline on memory sodium nitrate-induced consolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly less than in the control group （P 〈 0.01 ）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. ④ Synergistic effects of GSL and choline on ethanol-induced memory reconsolidation disorder in mice： During passive step down avoidance test, the number of error responses in the model group were significantly greater than in the control group （P 〈 0.01）; while the number of error responses in the combination group were significantly less than in the model group, GSL group, and choline group （P 〈 0.05-0.01）. The Q value was 〉 1 after combined administration, which suggests GSL and choline had synergistic effects. CONCLUSION： GSL and choline have synergistic effects on learning and memory functions.

Promotion of structural plasticity in area V2 of visual cortex prevents against object recognition memory deficits in aging and Alzheimer's disease rodents

Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.

Role of the hippocampus on learning and memory functioning and pain modulation

The hippocampus, an important part of the limbic system, is considered to be an important region of the brain for learning and memory functioning. Recent studies have demonstrated that synaptic plasticity is thought to be the basis of learning and memory functioning. A series of studies report that similar synaptic plasticity also exists in the spinal cord in the conduction pathway of pain sensation, which may contribute to hyperalgesia, abnormal pain, and analgesia. The synaptic plasticity of learning and memory functioning and that of the pain conduction pathway have similar mechanisms, which are related to the N-methyl-D-aspartic acid receptor. The hippocampus also has a role in pain modulation. As pain signals can reach the hippocampus, the precise correlation between synaptic plasticity of the pain pathway and that of learning and memory functioning deserves further investigation. The role of the hippocampus in processing pain information requires to be identified.

Kongsheng Zhenzhong pill's effect on the learning and memory ability and its neuroprotective effects in vascular dementia rats

Clinical reports have demonstrated that the Kongsheng Zhenzhong pill （KSZZP）, a classical prescription deriving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study, the expression of N-methyI-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentration of calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyI-D-aspartate receptor 1, nerve growth factor protein, and glial cell line-derived neurotrophic factor protein were detected with immunohistochemistry. We found that KSZZP could significantly decrease the expression of N-methyI-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glial cell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebral cortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitive impairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in the cognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.

Protective Effect of Ginkgo Biloba Leaf Extract on Learning and Memory Deficit Induced by Aluminum in Model Rats

Objective： To examine the protective effect of Ginkgo biloba leaf extract （GbE） on learning and memory deficit induced by aluminum chloride （AlCl3）, and explore its mechanisms. Methods： The rat models with learning and memory deficit were induced by administering via gastrogavage and drinking of AlCl3 solution. And the model rats were treated with GbE at the dose of 50, 100, 200 mg/kg every day for 2 months accompanied with drinking of AlCl3 solution, respectively. Their abilities of spatial learning and memory were tested by Morris water maze, and the acetylcholinesterase （ACHE） activity in serum was assayed with chemical method, the AChE expression in hippocampus was observed by immunohistochemistry assay, and then quantitative analysis was done by BI 2000 image analysis system. Results： Learning and memory deficit of rats could be induced by AlCl3 solution （P〈0.01）, and AChE expressions in rats hippocampus were increased （P〈0.01）; GbE ameliorated learning and memory deficit and reduced AChE expression in rats hippocampus in a dose-dependent manner, while GbE significantly increased serum AChE activity at the dose of 200 mg/kg each day （P〈0.05）. Conclusion： GbE can ameliorate learning and memory deficit induced by AlCl3, which may be due to its inhibition of the AChE expression in hippocampus.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory

Objective To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Methods Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. Results The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memory. Conclusion Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases.