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Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

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Chinese Medical Journal 2011年第10期124卷 1540-1544页

作者： JIANG Qing-song LIANG Zi-liang WU Min-Jie FENG Lin LIU Li-li ZHANG Jian-jun Department of Prosthodontics Beijing Stomatological Hospital and School of Stomatology Capital Medical University Beijing 100050 China Department of Pharmacology Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China School and Hospital of Stomatology Peking University Beijing 100081 China

Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 （SAMP8） mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals＇ body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor （BDNF） and the tropomyosin related kinase B （TrkB）, the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups （P〉0.05）. Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group （P〈0.05）; but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this effect was accompanied by significantly reduced BDNF e

关键词： molarless learning and memory water maze brain-derived neurotrophic Jactor TrkB

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Responses of CDKs and p53 in Delayed Ischemic Neuronal Death

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Journal of Nanjing Medical University 2002年第2期16卷 49-64页

作者：王伏虎 Neuroscience Research Institute University of Ottawa Ottawa Ontario Canada K1H 8M5

Stroke is a debilitating disease that affects millions each year. While in many cases cerebral ischemic injury can be limited by effective resuscitation or thrombolytic treatment, the injured neurons wither in a process known as delayed neuronal death (DND). Mounting evidence indicates that DND is not simply necrosis played out in slow motion but apoptosis is triggered. Of particular interest are two groups of signal proteins that participate in apoptosis cyclin dependent kinases (CDKs) and p53 among a myriad of signaling events after an ischemic insult. Recent investigations have shown that CDKs, a family of enzymes initially known for their role in cell cycle regulation, are activated in injured neurons in DND. As for p53, new reports suggest that its up regulation may represent a failed attempt to rescue injured neurons, although its up regulation was previously considered an indication of apoptosis. These observations thus rekindle an old quest to identify new neuroprotective targets to minimize the stroke damage. In this review, the author will examine the evidence that indicates the participation of CDKs and p53 in DND and then introduce pre clinical data to explore CDK inhibition as a potential neuroprotective target. Finally, using CDK inhibition as an example, this paper will discuss the pertinent criteria for a viable neuroprotective strategy for ischemic injury.

关键词： stroke cerebral ischemia excitotoxicity cyclin dependent kinases neuronal death apoptosis water maze retinoblastoma

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The role of MS/vDB-hippocampus cholinergic pathway in APP/PS1 mice at early stage

The role of MS/vDB-hippocampus cholinergic pathway in APP/PS...

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中国神经科学学会第十二届全国学术会议

作者： Xi Chen Li Yang Cheng Long School of Life Sciences South China Normal University School of Psychology South China Normal University Institute of Brain Science and Rehabilitation Medicine South China Normal University

The two main pathological manifestation of Alzheimer’s disease（AD） are senile plaques（Aβ） and neurofibrillary tangle（the major component is the abnormally phosphorylated microtubule binding protein tau）. Although presenilin（PS） and apolipoprotein E（ApoE） are also of concern, the mainstream direction of AD research has been focused on the Aβand tau. However, there is growing evidence that abnormal synaptic transmission disorder before Aβphosphate deposition and tau in the pathological features of AD in the central nervous system, the damage of cholinergic synaptic activity is particularly significant. The studies in AD patients also found that synaptic damage and dysfunction were the major factors affecting dementia, and that the association with cognitive impairment was more pronounced than amyloid plaques and neuronal loss. This suggests that there may be other mechanisms mediated by early onset AD. Neurons in the medial septum（MS） and vertical diagonal band of Broca（v DB） predominantly extend their axons to the hippocampus, forming the MS/v DB-hippocampal pathway, which play an important role in spatial memory. So,we study on whether young AD mice show cognitive behavioral abnormalities and what the role of cholinergic system plays in it. Material 3.5-5 month-old APP/PS1 mice and age-matched littermate wild-type mice were used. APP/PS1 mice expressing mouse/human chimeric APP gene（APPswe） and mutant PSEN1（Delta E9）, suitable for the study of AD effect especially in early stage of neurodegeneration and synaptic activity disorder, is an ideal animal model of internationally recognized, widely used in research related to the AD. According to reports, APP/PS1 mice showed decreased learning ability with increasing age, it is similar to AD cognitive impairment, moreover, the structure and function of synaptic connections in the hippocampus of the brain are abnormal. Methods In vivo double channel extracellular recording and Morris water maze test were employed. Results（1） Confirmed the neurons in MS/v DB projected to

关键词： Alzheimer’s disease APP/PS1 mice water maze Ms/vDB-hippocampus extracellular recording

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Changes of NMDA receptor expression in rat hippocampal formation after establishment of spatial memory by different training modes

Changes of NMDA receptor expression in rat hippocampal forma...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Li ZHANG,Wei YU,Tai-Zhen HAN Department of Physiology and Pathophysiology,Medical School of Xi''an Jiaotong University,Xi''an 710061

＜正＞A number of studies during the past decades have suggested a critical role of glutamatergic N-methyl-Daspartate （NMDA） receptors in learning and memory processes.Induction of hippocampal long-term potentiation（LTP） has been shown to require the activation of NMDA receptors.On the other hand,antagonists of the NMDA receptors, such as AP5,MK-801,and phencyclidine（PCP） have been proved to block hippocampal LTP in vitro and to impair hippocampal-dependent behavior,for example,place and spatial learning.These findings have led to the suggestions that NMDA receptors play a critical role in cognitive functions involving corticohippocampal circuits and that mechanisms underlying LTP and the behavioral manifestations of spatial learning are related.But most research got the results through using antagonists of NMDA receptor or destroying the hippocampal structures.The training course of normal Morris water maze（MWM） lasts 4-6 d,then establishing long spatial memory.In these training,the roles of the times and the time courses of training are unaware.Here we have a question that decreasing the time course and increasing the frequency of training of MWM,could establish the long spatial memory.In the present study,three spatial memory training modes of MWM were used:spatial long-term memory training mode（LT group）,spatial short-term memory mode（ST group） and short reinforcing training mode（SRT group）.The characteristics of those memories established by different training modes were compared.The immunofluorescence histochemical staining technique was used to observe the changes of NMDA/NRl expression in the hippocampal formation in the three groups.The results showed that,during MWM training,no significant difference was found in the mean latency and the strategies to the target as well as the times crossing the target between the LT and SRT groups.The mean time remaining in the platform quadrant in LT group was significantly longer than that of SRT group.In addition,no significant difference of the intensity of NMDA/NR1 i

关键词： spatial learning and memory water maze immunofluorescence hippocampal formation NMDA receptor

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Functional dissociation between the medial and the lateral entorhinal cortex of the rat in spatial navigation

Functional dissociation between the medial and the lateral e...

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中国神经科学学会第十届全国学术会议

作者： Wei-Ning ZHANG Yan XU Hong-Qun DING Chuan-Xiu BIAN Joram Feldon School of Medical Science ＆ Laboratory Medicine Jiangsu University

Objective Lesion studies in rats have indicated that the entorhinal cortex（EC） is involved in spatial learning and memory.The entorhinal cortex is regarded as an interface between the hippocampus and neocortex and its essential role is to support normal hippocampal-dependent functions,such as memory of spatial information.However,the exact characteristics of deficits following entorhinal cortex damage have not been fully described.The present study investigated,in Wistar rats,the effects of temporary inhibition of the medial or lateral entorhinal cortex on the retrieval of a well-learned response pattern and the reversal learning（new learning） of the location of an escape platform in the water maze.Methods Rats were bilaterally infused muscimol（1 μg/0.5 μl,per side） into the medial or lateral entorhinal cortex and tested the spatial learning and memory in the water maze.Results Muscimol（1 μg/0.5 μl,per side）infusion into the medial,but not lateral,entorhinal cortex markedly impaired the retrieval of spatial memory,and failed to affect reversal learning in the water maze.This impairment was temporary,such that the deficits in retrieval of spatial memory were restricted to the day of infusion.Conclusion Our data demonstrates that retrieval of spatial memory requires the involvement of neuronal activity of the medial but not lateral entorhinal cortex,suggesting a functional dissociation between the medial and lateral entorhinal cortex in spatial navigation.

关键词： entorhinal cortex muscimol temporary inhibition spatial learning and memory water maze

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Application of memantine hydrochloride in depression-model rats

Application of memantine hydrochloride in depression-model r...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Mei-Na QUAN~1,Shuang LIANG~2,Tao ZHANG~2,Zhuo YANG~(1,*) 1 Laboratory of Neurophysiology,Medical School,Nankai University,Tianjin 300071,China 2 Laboratory of Bioinformatics,Life Science Institude,Nankai University,Tianjin 300071,China

＜正＞Objective This study was designed to establish an animal model of depression,and using physiological, behavioral and electrophysiological methods to explore the pathogenesis of depression and to assess possible antidepressant effects of Memantine hydrochloride（HCL）,a selective N-methyl-D-aspartate（NMD A） antagonist,in this animal model.Methods The animal model of depression was established in male Wistar rats by combining isolation rearing with chronic unpredictable mild stress（CUMS）.Memantine HCL（20 mg/kg） was administered intraperitoneally from the second day of establishing depression model,for 21 d,until the first day of water maze experiments.The rats’ physiological status was observed by their weights and sucrose consumption.Behavioral change was observed by water maze test.Electrophysiological change was tested by recording long-term potentiation（LTP） from thalamus to prefrontal cortex.Results （1） Compared with normal group,rats’ weight increase and sucrose consumption was statistically lower in CUMS model group and Memantine HCL-treated group.（2） In the water maze test,the mean escape latency（EL） of the first period of Oriented Navigation Training（ONT） was significantly prolonged in CUMS model group and Memantine HCL-treated group as compared with that of normal group.EL of the second and third periods of ONT was significantly prolonged in Memantine HCL-treated group as compared with those of normal group and CUMS model group.（3） LTP test showed that excitatory postsynaptic potential（PSP） slopes were statistically different among three groups.CUMS model group had the lowest slopes and normal group had the highest slopes.Conclusion Animal model of depression can be established successfully by isolation rearing combined with chronic unpredicted mild stress.In a 21-d trial,Memantine in the dose of 20 mg/kg was not effective in the treatment of depression,but it could improve synaptic plasticity in prefrontal cortex in model rats.

关键词： depression Memantine HCL isolation rearing CUMS water maze LTP

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