资源描述
单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,文档之家-http:/ Traumatic Stress Disorder),创伤后应激障碍，指对创伤等严重应激因素的一种异常精神反应。（是指突发性、威胁性或灾难性生活事件导致个体延迟出现和长期持续存在的精神障碍,其临床表现以再度体验）又称延迟性心因性反应,是指由异乎寻常的威胁性或灾难引起的一系列病态。,2,文档之家-http:/ acid,，,KA,）合称非,NMDA,受体。近年来的研究又发现，,QA,（使君子酸受体）实际激活了两型受体，即离子型的,氨基羟甲基异恶唑丙酸（,AMPA,）受体,和,代谢型谷氨酸受体（,mGluR,）。,随后又发现一种位于突触前膜上的新型受体，即,L2,氨基,4,磷酰基丁酸（,LAP4,）受体,，它属于突触前自身受体，与,G,蛋白耦联，激活磷脂酶,A,，催化磷脂酰肌醇水解为肌醇三磷酸（,IP3,）和甘油二酯（,DAG,）作为第二信使，再引起一系列生化反应。,10,文档之家-http:/ dependent protein kinase,一,CaMK,）参与形成早期记忆；而将短期记忆转换为长期记忆必需联合赖氨酸激酶和丝氨酸,L/,苏氨酸激酶（,MAPK,）；蛋白激酶,A,（,PKA,）和蛋白激酶,C,（,PKC,）也与,LTP,密切相关,【4】,。,CaMKII,是突触后致密物质,(postsynaptic density,，,PSD),的重要组成成分，在脑内分布的主要为,和,亚单位，被,Ca2+,激活的,CaMK II,主要通过磷酸化突触前后的靶蛋白，例如,AMPA,、突触素,I(synapsin I),和微管相关蛋白,(microtubule assoeiated protein2,，,MAP2),来参与,LTP,的诱导和维持。,11,文档之家-http:/ PTSD,大鼠急性期杏仁核,LTP,受到抑制；,PTSD,大鼠后期杏仁核,LTP,增强，导致恐惧增强，揭示杏仁核功能异常是,PTSD,的部分发病机制。,15,文档之家-http:/ 7d,时杏仁核,LTP,增强，恐惧反应增强，之后逐渐恢复至正常。,PTSD,样大鼠海马神经元,LTP,抑制,，提示可能与,PTSD,所致,记忆失常,机制相关。,16,文档之家-http:/ kinase II,），或简写成,CaMKII,，是一种信号分子，在诱导长时程增强,(Long-term potentiation,，,LTP),的过程中起着关键的作用。之前的研究发现，长时程增强在一些类型的学习、记忆中可以增强神经元间的交流活动。杜克大学的,Ryohei Yasuda,研究小组开发出一种新的成像技术，能够在,LTP,过程中跟踪单一突触内,CaMKII,的激发。,单突触,LTP,过程中,CaMKII,的激发过程,22,文档之家-http:/ dependent protein kinase,一,CaMK),具有这一特性，当,Ca2+,内流时能够使,CaMK II,磷酸化而被激活，活化的,CaMK II,自身磷酸化，而且当,Ca2+,下降后,CaMK II,的活性仍能保持其状态，因此，人们认为,CaMK,可能是记忆的分子开关。,23,文档之家-http:/ 25】,，进而增加海马和大脑皮层,NMDA,受体,NRl,和,NR2B,亚基的磷酸化水平,【26】,，并且增加受体离子通道的开放和信息传递,【27】,。,24,文档之家-http:/ U,Huang YY,Kandel ER.Effects of Camp simulate a late stage of LTP in hippocampal CA1 neuronsJ.Science,1993,260:16611664.,Platerik J,Kuramoto N,Yoneda Y.2000.Molecular mechanisms associated with longterm consolidation of the NMDA signals.Life Science,67(4):64335,Balck IB.1999.Trophic regulation of synaptic plasticity.Journal of Neurobiology,41(1):1018,Mu JS,Li WP,Yao ZB,et al.1999.Deprivation of endogenous brain-derived neurotrophic factors results in impairment of spatial learning and memory in adult rats.Brain Reserve,835(2):259265,26,文档之家-http:/ ML,，,Charney DS,，,Deutch AY,Neurobiological and clinical consequences,of stress,：,from normal adaptation to posttranmatic stress disorderM,Philadelpgia,：,Lippincott Raven,1995,，,1535,8.Nutt D,，,Davidson JRL,Zohar J,Posttraumtic stess disorder,：,diagnosis,，,management and treatmentM,London,：,Martin Dunitz Ltd,2000,，,1-99,9.Vanitallie TB.Stress:a risk factor for serious illnessJ.Metabolism,2002,51:40-45,10.Wang M,Chen J,Ruan DY,et al.The influence of developmental period of aluminum,exposure on synaptic plasticity in the adult rat dentate gyrus in vivo.,Neuroscience,2002,113:411-419,11.Sun Shi-lei,MA Guang-yu,LI Hua Bachelor,et al.Effect of naloxone on,aluminum-induced learning and memory impairment in rats.,Neurol India,2005,53:79-82,12.,郑浩，李晓波，李淼，等纳米氧化铝对大鼠学习记忆能力的影响,中国行为医学科学，,2008,，,17,：,202-203,，,13.Platt B,，,Haas H,，,Busselberg D,Aluminium reduces glutamate-activated currents,of rathippocampal neurones,Neuroreport.1994,，,5,：,2329-2332,V,14.Hermencgildo C,，,Saez R,，,Minoia C,，,et al,，,Chronic exposure to aluminium,impairs the glutamate-nitric oxide-cyclic GMP pathway in the rat in vivo,Ncurochem Int,，,1999,，,34,：,245-253,27,文档之家-http:/ 国公 共卫生，,2006,，,22,：,1464-1466,16.,邢伟，王彪，郝风进，等慢性铝暴露对大鼠海马神经元,PKC,、,CaMK,、,Ng,的影响中国生物化学与分子生物学学报,2007,，,23:410-414,17.,邢伟，王彪，许金华，等慢性染铝大鼠海马,PKC,、,MAPK,活力与,LTP,的相关性，毒理学杂志，,2007,，,21,：,102-104,18.,宗志红陈井阳，孟晓娜，等铝暴露对大鼠海马,CAI,区长时程增强及,-CaMK,活性的影响中国医科大学学报，,2007,，,36,：,636-637,19.,刘慧慧，孙沾，邢伟，等母体慢性铝暴露对子代鼠海马细胞内,Ca2+,浓度及记忆行为的影响中国药理学通报，,2007,23,：,912-916,20.,南娟，刘慧慧，杜艳霞，等出生前后慢性铝暴露对大鼠学习记忆及海马内,NO,、,nNOS,的影响中国药理学通报，,2007,，,23,：,1152,一,1155,21.,殷文娟，李新毅，祁金顺,CaMK II,磷酸化介导海马长时程增强的诱导及淀粉样,8,蛋白引起的长时程增强伤害,J,中西医结合心脑血管病杂志，,2008,，,6(5),：,557559,22.Vaynman S,，,Ying Z and GomezPinilla,Interplay betweenbrainderived neurotrophic factor signal transduction modulators in the regulation of the effects of exercise on synaptic plasticityJ,Neuroscience,，,2003,，,122,：,657657,23.Dietrich M O,，,Mantese C E,，,Powiuncula L O,，,et aL Exerciseaffects glutamate receptors in postsynaptic densities from cortical mice brainJ,Brain Research,，,2005,，,1065,：,2025,28,文档之家-http:/ A Neeper,，,Femando G6mezPiniUa,，,James Choi,，,et a1,Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brainJ,Brain Research,，,1996,，,726,：,4956,25.Adlard Paul A,，,Victoria M Perreau,，,Christie EC,，,et al.Thetimecourse of induction of brainderived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exerciseJ,Neuroscience Letters,，,2004,，,363(1),：,4348,26.Lin S Y,，,Wu K,Levine E S,，,et a1,BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densitiesJ,Brain Res Mol Brain Res,，,1998,，,55,：,2027,27.Levine E S,，,Kolb J E,Brainde rived neurotrophic factor increasesactivity of NR2B containing NmethylDaspartate receptors in excised patches from hippocampal neuronsJ,J Neurosci Res,，,2000,，,62,：,357362,29,文档之家-http:/
展开阅读全文