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 rode...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.展开更多
Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this stud...Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM...F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.展开更多
汽车路噪的分析与治理是NVH(Noise,Vibration And Harshness)工作的重要组成部分。由于路噪的产生机理复杂,建立机理模型较困难,故引入数据驱动方法对路噪进行研究。首先,对路噪影响因素进行剖析,界定出具有显著性的影响因素。在此基础...汽车路噪的分析与治理是NVH(Noise,Vibration And Harshness)工作的重要组成部分。由于路噪的产生机理复杂,建立机理模型较困难,故引入数据驱动方法对路噪进行研究。首先,对路噪影响因素进行剖析,界定出具有显著性的影响因素。在此基础上,运用长短时记忆神经网络算法(LSTM)揭示路噪与其影响因素间的复杂非线性关系,建立路噪预测模型。进而在粗糙沥青路面分别以40 km/h、60 km/h的车速工况采集悬架相关部件振动数据和驾驶员右耳畔噪声数据,以获得样本用于路噪模型的训练和检验。并采用Mixup数据增强策略合成新的样本,从而使样本量不足状况得到改善。进一步,对LSTM路噪预测模型进行检验与分析,测试结果均方误差为0.076 2,表明预测效果良好,证明所提方法的有效性。同时,将BPNN、SVR与LSTM预测方法进行比较,发现LSTM路噪预测模型精度更高,泛化能力更好,从而证明该方法的优越性。展开更多
Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper tr...Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced world- wide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.展开更多
Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet...Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.展开更多
The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we in...The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these populations.展开更多
Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extrac...Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.展开更多
BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheime...BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P 〈 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P 〈 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer's disease. The therapeutic effects of PNS for Alzheimer's disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.展开更多
Statistics of languages are usually calculated by counting characters, words, sentences, word rankings. Some of these random variables are also the main “ingredients” of classical readability formulae. Revisiting th...Statistics of languages are usually calculated by counting characters, words, sentences, word rankings. Some of these random variables are also the main “ingredients” of classical readability formulae. Revisiting the readability formula of Italian, known as GULPEASE, shows that of the two terms that determine the readability index G—the semantic index , proportional to the number of characters per word, and the syntactic index GF, proportional to the reciprocal of the number of words per sentence—GF is dominant because GC is, in practice, constant for any author throughout seven centuries of Italian Literature. Each author can modulate the length of sentences more freely than he can do with the length of words, and in different ways from author to author. For any author, any couple of text variables can be modelled by a linear relationship y = mx, but with different slope m from author to author, except for the relationship between characters and words, which is unique for all. The most important relationship found in the paper is that between the short-term memory capacity, described by Miller’s “7 ? 2 law” (i.e., the number of “chunks” that an average person can hold in the short-term memory ranges from 5 to 9), and the word interval, a new random variable defined as the average number of words between two successive punctuation marks. The word interval can be converted into a time interval through the average reading speed. The word interval spreads in the same range as Miller’s law, and the time interval is spread in the same range of short-term memory response times. The connection between the word interval (and time interval) and short-term memory appears, at least empirically, justified and natural, however, to be further investigated. Technical and scientific writings (papers, essays, etc.) ask more to their readers because words are on the average longer, the readability index G is lower, word and time intervals are longer. Future work done on ancient languages, such as the classical Greek and Latin Literatures (or modern languages Literatures), could bring us an insight into the short-term memory required to their well-educated ancient readers.展开更多
Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that...Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer's disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer's disease.展开更多
In this paper, we discuss questions of creating an electronic intellectual analogue of a human being. We introduce a mathematical concept of stimulus generating emotions. We also introduce a definition of logical thin...In this paper, we discuss questions of creating an electronic intellectual analogue of a human being. We introduce a mathematical concept of stimulus generating emotions. We also introduce a definition of logical thinking of robots and a notion of efficiency coefficient to describe their efficiency of rote (mechanical) memorizing. The paper proves theorems describing properties of permanent conflicts between logical and emotional thinking of robots with a nonabsolute rote memory.展开更多
Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefor...Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.展开更多
自Oxford Advanced Learner's Dictionary of Current English(以下简称《牛津》)和Zongman Dictionary of Contem porary English(以下简称《朗曼》)问世以来,它们在上世纪下半叶中一直风行全世界。这两本英语学习者词典的目的在...自Oxford Advanced Learner's Dictionary of Current English(以下简称《牛津》)和Zongman Dictionary of Contem porary English(以下简称《朗曼》)问世以来,它们在上世纪下半叶中一直风行全世界。这两本英语学习者词典的目的在于解决外国研习英语者所面临的特殊困难。展开更多
Grover’s search algorithm is one of the most significant quantum algorithms,which can obtain quadratic speedup of the extensive search problems.Since Grover's search algorithm cannot be implemented on a real quan...Grover’s search algorithm is one of the most significant quantum algorithms,which can obtain quadratic speedup of the extensive search problems.Since Grover's search algorithm cannot be implemented on a real quantum computer at present,its quantum simulation is regarded as an effective method to study the search performance.When simulating the Grover's algorithm,the storage space required is exponential,which makes it difficult to simulate the high-qubit Grover’s algorithm.To this end,we deeply study the storage problem of probability amplitude,which is the core of the Grover simulation algorithm.We propose a novel memory-efficient method via amplitudes compression,and validate the effectiveness of the method by theoretical analysis and simulation experimentation.The results demonstrate that our compressed simulation search algorithm can help to save nearly 87.5%of the storage space than the uncompressed one.Thus under the same hardware conditions,our method can dramatically reduce the required computing nodes,and at the same time,it can simulate at least 3 qubits more than the uncompressed one.Particularly,our memory-efficient simulation method can also be used to simulate other quantum algorithms to effectively reduce the storage costs required in simulation.展开更多
On the basis of explaining goals of building temple gardens,Gu Dongyang’s Memorial Temple in Wuxi City was taken for example to analyze its gardening arts from the perspective of water layout,stone layout,building an...On the basis of explaining goals of building temple gardens,Gu Dongyang’s Memorial Temple in Wuxi City was taken for example to analyze its gardening arts from the perspective of water layout,stone layout,building and plant design,and elaborate its cultural connotations from decorative symbols of its architectural components.It was concluded that Gu Dongyang’s Memorial Temple,in spite of its small size and plain style,had profound historical background and high referential value for furthering the study on temple gardens in the south of the Yangtze River.展开更多
Associative memory, one of the major cognitive functions in the hippocampal CA3 region, includes auto-associative memory and hetero-associative memory. Many previous studies have shown that Alzheimer's disease (AD)...Associative memory, one of the major cognitive functions in the hippocampal CA3 region, includes auto-associative memory and hetero-associative memory. Many previous studies have shown that Alzheimer's disease (AD) can lead to loss of functional synapses in the central nervous system, and associative memory functions in patients with AD are often impaired, but few studies have addressed the effect of AD on hetero-associative memory in the hippocampal CA3 region. In this study, based on a simplified anatomical structure and synaptic connections in the hippocampal CA3 region, a three-layered Hopfield-like neural network model of hippocampal CA3 was proposed and then used to simulate associative memory functions in three circumstances: normal, synaptic deletion and synaptic compensation, according to Ruppin's synaptic deletion and compensation theory. The influences of AD on hetero-associative memory were further analyzed. The simulated results showed that the established three-layered Hopfield-like neural network model of hippocampal CA3 has both auto-associative and hetero-associative memory functions. With increasing synaptic deletion level, both associative memory functions were gradually impaired and the mean firing rates of the neurons within the network model were decreased. With gradual increasing synaptic compensation, the associative memory functions of the network were improved and the mean firing rates were increased. The simulated results suggest that the Hopfield-like neural network model can effectively simulate both associative memory functions of the hippocampal CA3 region. Synaptic deletion affects both auto-associative and hetero-associative memory functions in the hippocampal CA3 region, and can also result in memory dysfunction. To some extent, synaptic compensation measures can offset two kinds of associative memory dysfunction caused by synaptic deletion in the hippocampal CA3 area.展开更多
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘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.
基金supported by the National Natural Science Foundation of China, Nos. 82060727 (to FJ), 81660599 (to FJ)the National Innovation Training Project for College Students, No. 201910661009 (to FJ)the Science and Technology Cooperation Project of Zunyi Science and Technology Bureau and Zunyi Medical University, No. (2019) 47 (to XLF)
文摘Icariin,a major prenylated flavonoid found in Epimedium spp.,is a bioactive constituent of Herba Epimedii and has been shown to exert neuroprotective effects in experimental models of Alzheimer’s disease.In this study,we investigated the neuroprotective mechanism of icariin in an APP/PS1/Tau triple-transgenic mouse model of Alzheimer’s disease.We performed behavioral tests,pathological examination,and western blot assay,and found that memory deficits of the model mice were obviously improved,neuronal and synaptic damage in the cerebral cortex was substantially mitigated,and amyloid-βaccumulation and tau hyperphosphorylation were considerably reduced after 5 months of intragastric administration of icariin at a dose of 60 mg/kg body weight per day.Furthermore,deficits of proteins in the insulin signaling pathway and their phosphorylation levels were significantly reversed,including the insulin receptor,insulin receptor substrate 1,phosphatidylinositol-3-kinase,protein kinase B,and glycogen synthase kinase 3β,and the levels of glucose transporter 1 and 3 were markedly increased.These findings suggest that icariin can improve learning and memory impairments in the mouse model of Alzheimer’s disease by regulating brain insulin signaling and glucose transporters,which lays the foundation for potential clinical application of icariin in the prevention and treatment of Alzheimer’s disease.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
文摘F_(10.7)指数是太阳活动的重要指标,准确预测F_(10.7)指数有助于预防和缓解太阳活动对无线电通信、导航和卫星通信等领域的影响.基于F_(10.7)射电流量的特性,在双向长短时记忆网络(Bidirectional Long Short-Term Memory Network,BiLSTM)基础上融入注意力机制(Attention),提出了一种基于BiLSTM-Attention的F_(10.7)预报模型.在加拿大DRAO数据集上其平均绝对误差(MAE)为5.38,平均绝对百分比误差(MAPE)控制在5%以内,相关系数(R)高达0.987,与其他RNN模型相比拥有优越的预测性能.针对中国廊坊L&S望远镜观测的F_(10.7)数据集,提出了一种转换平均校准(Conversion Average Calibration,CAC)方法进行数据预处理,处理后的数据与DRAO数据集具有较高的相关性.基于该数据集对比分析了RNN系列模型的预报效果,实验结果表明,BiLSTM-Attention和BiLSTM两种模型在预测F_(10.7)指数方面具有较好的优势,表现出较好的预测性能和稳定性.
文摘Alzheimer's disease is an age-related neurodegenerative disorder characterized by memory deficits. Various studies have been carried out to find therapeutic approaches for Alzheimer's disease. However, the proper treatment option is still not available. There is no cure for Alzheimer's disease, but symptomatic treatment may improve the memory and other dementia related problems. Traditional medicine is practiced world- wide as memory enhancer since ancient times. Natural therapy including herbs and medicinal plants has been used in the treatment of memory deficits such as dementia, amnesia, as well as Alzheimer's disease since a long time. Medicinal plants have been used in different systems of medicine, particularly Unani system of medicines and exhibited their powerful roles in the management and cure of memory disorders. Most of herbs and plants have been chemically evaluated and their efficacy has also been proven in clinical trials. However, the underlying mechanisms of actions are still on the way. In this paper, we have reviewed the role of different medicinal plants that play an important role in the treatment of Alzheimer's disease and memory deficits using conventional herbal therapy.
文摘Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.
基金supported by the National Natural Science Foundation of China,No.81371107,81470760the Natural Science Foundation of Guangdong Province in China,No.S2013010015888+1 种基金the Foundation of Open Laboratory of Sun Yat-sen University in China,No.KF201312a grant from Translational Medicine Center,Guangdong Department of Science&Technology,No.2011A080300002
文摘The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and indicate that tooth extraction should be avoided in these populations.
基金financially supported by the National Science and Technology Major Project for New Drug Creation Program by the Ministry of Science and Technology No.2009ZX09502-014
文摘Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.
基金the National Natural Science Foundation of China, No: 30560189
文摘BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer's disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β -amyloid (A β ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of A β 1-40, A β 1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content ofApp, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P 〈 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of A β 1-40, A β 1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P 〈 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer's disease. The therapeutic effects of PNS for Alzheimer's disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A.
文摘Statistics of languages are usually calculated by counting characters, words, sentences, word rankings. Some of these random variables are also the main “ingredients” of classical readability formulae. Revisiting the readability formula of Italian, known as GULPEASE, shows that of the two terms that determine the readability index G—the semantic index , proportional to the number of characters per word, and the syntactic index GF, proportional to the reciprocal of the number of words per sentence—GF is dominant because GC is, in practice, constant for any author throughout seven centuries of Italian Literature. Each author can modulate the length of sentences more freely than he can do with the length of words, and in different ways from author to author. For any author, any couple of text variables can be modelled by a linear relationship y = mx, but with different slope m from author to author, except for the relationship between characters and words, which is unique for all. The most important relationship found in the paper is that between the short-term memory capacity, described by Miller’s “7 ? 2 law” (i.e., the number of “chunks” that an average person can hold in the short-term memory ranges from 5 to 9), and the word interval, a new random variable defined as the average number of words between two successive punctuation marks. The word interval can be converted into a time interval through the average reading speed. The word interval spreads in the same range as Miller’s law, and the time interval is spread in the same range of short-term memory response times. The connection between the word interval (and time interval) and short-term memory appears, at least empirically, justified and natural, however, to be further investigated. Technical and scientific writings (papers, essays, etc.) ask more to their readers because words are on the average longer, the readability index G is lower, word and time intervals are longer. Future work done on ancient languages, such as the classical Greek and Latin Literatures (or modern languages Literatures), could bring us an insight into the short-term memory required to their well-educated ancient readers.
基金supported by the National Natural Science Foundation of China,No.81303097,81373794
文摘Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer's disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer's disease.
文摘In this paper, we discuss questions of creating an electronic intellectual analogue of a human being. We introduce a mathematical concept of stimulus generating emotions. We also introduce a definition of logical thinking of robots and a notion of efficiency coefficient to describe their efficiency of rote (mechanical) memorizing. The paper proves theorems describing properties of permanent conflicts between logical and emotional thinking of robots with a nonabsolute rote memory.
文摘Alzheimer’s disease (AD) is the most prominent dementia-related disease and characterized by the presence of insoluble amyloid beta peptide (Aβ) fibers in or around the brain neurons of the affected person. Therefore, agent(s) capable of inhibiting brain amyloid deposition might delay the occurrence or retard the progress forwards of AD and related neurobehavioral symptoms. Here, we report whether, chronic oral administration of Syzygium cumini (locally known as Jam)-seed extract exerts protection against the progressive cognitive decline in the Aβ1-40-infused AD model rats. After 12 weeks of feeding with S. cumini seed extract (at 300 mg/kg BW), we evaluated the learning-related memory of the rats by 8-arm radial maze task, where we determined two types of memory errors, namely reference memory errors (RMEs) and working memory errors (WMEs). After completion of memory tests, rats were sacrificed and the levels of lipid peroxide (LPO), the Aβ1-40-burden, Aβ1-40-oligomers, proinflammatory TNFα, brain derived neurotrophic factor (BDNF), Tyrosine-kinase B (TrkB), postsynaptic-density protein 95 (PSD-95) and Synapse-associated protein (SNAP-25) were determined in the corticohippocampal tissues of the brain. In addition, in vitro antioxidative effects of S. cumini seed extract were evaluated. The oral administration of S. cumini extract significantly increased the memory-related learning ability of the AD model rats, concomitantly with reductions in the levels of corticohippocampal Aβ1-40-burden and Aβ1-40-oligomers. Furthermore, the extract suppressed the levels of TNFα and LPO in the corticohippocampal tissues of the AD rats and also the later in the plasma, suggesting an anti-oxidative and anti-inflammatory activities of the S. cumini extract in the brains of AD model rats. S. cumini extract also increased the levels of brain cognition and memory-related proteins, including BDNF, TrKB, PSD-95 and SNAP-25. We thus suggest that S. cumini-seed extract could be used in neurobehavioral deficits and associated pathogenesis of Alzheimer’s disease.
文摘自Oxford Advanced Learner's Dictionary of Current English(以下简称《牛津》)和Zongman Dictionary of Contem porary English(以下简称《朗曼》)问世以来,它们在上世纪下半叶中一直风行全世界。这两本英语学习者词典的目的在于解决外国研习英语者所面临的特殊困难。
基金This work was supported by Funding of National Natural Science Foundation of China(Grant No.61571226,Grant No.61701229).
文摘Grover’s search algorithm is one of the most significant quantum algorithms,which can obtain quadratic speedup of the extensive search problems.Since Grover's search algorithm cannot be implemented on a real quantum computer at present,its quantum simulation is regarded as an effective method to study the search performance.When simulating the Grover's algorithm,the storage space required is exponential,which makes it difficult to simulate the high-qubit Grover’s algorithm.To this end,we deeply study the storage problem of probability amplitude,which is the core of the Grover simulation algorithm.We propose a novel memory-efficient method via amplitudes compression,and validate the effectiveness of the method by theoretical analysis and simulation experimentation.The results demonstrate that our compressed simulation search algorithm can help to save nearly 87.5%of the storage space than the uncompressed one.Thus under the same hardware conditions,our method can dramatically reduce the required computing nodes,and at the same time,it can simulate at least 3 qubits more than the uncompressed one.Particularly,our memory-efficient simulation method can also be used to simulate other quantum algorithms to effectively reduce the storage costs required in simulation.
文摘On the basis of explaining goals of building temple gardens,Gu Dongyang’s Memorial Temple in Wuxi City was taken for example to analyze its gardening arts from the perspective of water layout,stone layout,building and plant design,and elaborate its cultural connotations from decorative symbols of its architectural components.It was concluded that Gu Dongyang’s Memorial Temple,in spite of its small size and plain style,had profound historical background and high referential value for furthering the study on temple gardens in the south of the Yangtze River.
基金the National Natural Science Foundation of China,No.30870649the Natural Science Foundation of Tianjin,No.08JCYBJC03300
文摘Associative memory, one of the major cognitive functions in the hippocampal CA3 region, includes auto-associative memory and hetero-associative memory. Many previous studies have shown that Alzheimer's disease (AD) can lead to loss of functional synapses in the central nervous system, and associative memory functions in patients with AD are often impaired, but few studies have addressed the effect of AD on hetero-associative memory in the hippocampal CA3 region. In this study, based on a simplified anatomical structure and synaptic connections in the hippocampal CA3 region, a three-layered Hopfield-like neural network model of hippocampal CA3 was proposed and then used to simulate associative memory functions in three circumstances: normal, synaptic deletion and synaptic compensation, according to Ruppin's synaptic deletion and compensation theory. The influences of AD on hetero-associative memory were further analyzed. The simulated results showed that the established three-layered Hopfield-like neural network model of hippocampal CA3 has both auto-associative and hetero-associative memory functions. With increasing synaptic deletion level, both associative memory functions were gradually impaired and the mean firing rates of the neurons within the network model were decreased. With gradual increasing synaptic compensation, the associative memory functions of the network were improved and the mean firing rates were increased. The simulated results suggest that the Hopfield-like neural network model can effectively simulate both associative memory functions of the hippocampal CA3 region. Synaptic deletion affects both auto-associative and hetero-associative memory functions in the hippocampal CA3 region, and can also result in memory dysfunction. To some extent, synaptic compensation measures can offset two kinds of associative memory dysfunction caused by synaptic deletion in the hippocampal CA3 area.