电针对SAMP8小鼠海马神经元突触超微结构的影响研究
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摘要
目的研究电针对SAMP8小鼠海马神经元突触大体形态、突触界面曲率、突触后致密物、突触间隙等突触超微结构的影响,从突触形态可塑性的角度探讨电针治疗AD的部分作用机制。
方法以SAMP8小鼠作为阿尔茨海默氏病(Alzheimer's disease,AD)动物模型,根据“补肾通督、醒神益智”的治疗原则,电针“百会”、“涌泉”穴,每日一次,共治疗21天。以Morris水迷宫测试小鼠学习记忆能力的变化,评价电针对AD的治疗效应;用电镜观察海马神经元突触大体形态、突触界面曲率、突触后致密物厚度和突触间隙宽度的变化。
结果1.与模型组相比,模针组平均逃避潜伏期缩短(P＜0.05);模针组(38.55±3.59s)在原平台所在象限停留的时间较模型组(30.59+6.02s)延长(P＜0.05);2.与模型组相比,模针组突触形态较清楚,突触囊泡增多;模针组突触后致密物(76.928±25.236nm)较模型组(65.371±24.219nm)增厚(P＜0.05);突触间隙宽度(25.941±6.217nm)较模型组(29.161±7.830nm)减小(P＜0.05);突触界面曲率(1.083±0.049)较模型组(1.062±0.048)变化不明显,呈增大趋势(P＞0.05)。
结论1.电针能在一定程度上改善SAMP8小鼠学习记忆能力;2.电针对海马神经元突触形态有一定影响,能使突触后致密物增厚,突触间隙宽度变窄,突触界面曲率呈增大趋势,促进突触形态可塑性的发挥;3.电针改善SAMP8小鼠学习记忆能力的治疗效应可能与促进海马神经元突触形态可塑性的发挥有关。
Objective To study the influence of electro-acupuncture(EA) therapy on the general morphous of hippocampal synapse,the curvature of synaptic interface,the post synaptic density(PSD),the synaptic cleft and other synaptic ultrastructures of SAMP8 rat's hippocampal neuron to explore the partial curative mechanism of EA therapy for Alzheimer's disease(AD) in the perspective of synaptic morphological plasticity.
Methods According to the therapeutic principle of "Tonifying kidney and activating Du meridian to refresh the mind and promote intelligence", SAMP8 rats were treated with EA therapy on "Baihui(Du20)" and "Yongquan(Kidneyl)".The treatment was applied once daily and totally for 21 days.The changes of learning and memory abilities of these animal models were observed and recorded by Morris water maze to evaluate the curative effect of EA therapy.The changes of the general morphous of hippocampal synapse,the curvature of synaptic interface, the thickness of post synaptic density and the width of synaptic cleft were observed by electron microscope.
Results 1.Compared to control group,the average escape latency of EA group was decreased(P＜0.05);Compared to control group(30.59±6.02s),the time of swim in primary platform quadrant of EA group(38.55±3.59s) were increased(P＜0.05).2.Compared to control group, structure of neural synapse in EA group were comparatively clear and complete,the thickness of PSD in EA group was increased(P＜0.05),the width of synaptic cleft in EA group was decreased(P＜0.05) and the curvature of the synaptic interface in EA group had no obvious changes and only shown increasing-tendency(P＞0.05).
Conclusion 1.EA therapy could improve the learning and memory abilities of SAMP8 rats in a certain extent.2.EA therapy could influence morphological plasticity in hippocampal synapse by thickening PSD, narrowing synaptic cleft and so on.3.The curative mechanism of EA therapy may be related to enhancing synaptic morphological plasticity of hippocampal neurons.
方法以SAMP8小鼠作为阿尔茨海默氏病(Alzheimer's disease,AD)动物模型,根据“补肾通督、醒神益智”的治疗原则,电针“百会”、“涌泉”穴,每日一次,共治疗21天。以Morris水迷宫测试小鼠学习记忆能力的变化,评价电针对AD的治疗效应;用电镜观察海马神经元突触大体形态、突触界面曲率、突触后致密物厚度和突触间隙宽度的变化。
结果1.与模型组相比,模针组平均逃避潜伏期缩短(P＜0.05);模针组(38.55±3.59s)在原平台所在象限停留的时间较模型组(30.59+6.02s)延长(P＜0.05);2.与模型组相比,模针组突触形态较清楚,突触囊泡增多;模针组突触后致密物(76.928±25.236nm)较模型组(65.371±24.219nm)增厚(P＜0.05);突触间隙宽度(25.941±6.217nm)较模型组(29.161±7.830nm)减小(P＜0.05);突触界面曲率(1.083±0.049)较模型组(1.062±0.048)变化不明显,呈增大趋势(P＞0.05)。
结论1.电针能在一定程度上改善SAMP8小鼠学习记忆能力;2.电针对海马神经元突触形态有一定影响,能使突触后致密物增厚,突触间隙宽度变窄,突触界面曲率呈增大趋势,促进突触形态可塑性的发挥;3.电针改善SAMP8小鼠学习记忆能力的治疗效应可能与促进海马神经元突触形态可塑性的发挥有关。
Objective To study the influence of electro-acupuncture(EA) therapy on the general morphous of hippocampal synapse,the curvature of synaptic interface,the post synaptic density(PSD),the synaptic cleft and other synaptic ultrastructures of SAMP8 rat's hippocampal neuron to explore the partial curative mechanism of EA therapy for Alzheimer's disease(AD) in the perspective of synaptic morphological plasticity.
Methods According to the therapeutic principle of "Tonifying kidney and activating Du meridian to refresh the mind and promote intelligence", SAMP8 rats were treated with EA therapy on "Baihui(Du20)" and "Yongquan(Kidneyl)".The treatment was applied once daily and totally for 21 days.The changes of learning and memory abilities of these animal models were observed and recorded by Morris water maze to evaluate the curative effect of EA therapy.The changes of the general morphous of hippocampal synapse,the curvature of synaptic interface, the thickness of post synaptic density and the width of synaptic cleft were observed by electron microscope.
Results 1.Compared to control group,the average escape latency of EA group was decreased(P＜0.05);Compared to control group(30.59±6.02s),the time of swim in primary platform quadrant of EA group(38.55±3.59s) were increased(P＜0.05).2.Compared to control group, structure of neural synapse in EA group were comparatively clear and complete,the thickness of PSD in EA group was increased(P＜0.05),the width of synaptic cleft in EA group was decreased(P＜0.05) and the curvature of the synaptic interface in EA group had no obvious changes and only shown increasing-tendency(P＞0.05).
Conclusion 1.EA therapy could improve the learning and memory abilities of SAMP8 rats in a certain extent.2.EA therapy could influence morphological plasticity in hippocampal synapse by thickening PSD, narrowing synaptic cleft and so on.3.The curative mechanism of EA therapy may be related to enhancing synaptic morphological plasticity of hippocampal neurons.
引文
1.St George—Hyslop PH,Petit A.Molecular biology and genetics of Alzheimer's disease.C R Biol,2005,328(2):119-130
2.张均田.老年痴呆的发病机制及防治药物.医药导报,2002,21(8):469-471
3.何跃.老年性痴呆患病率及神经生化标志物的研究现状.中国临床康复,2005,9(4):143-145
4.盛树力,主编.老年性痴呆的治疗与护理.北京:科学文献出版社.2000:232
5.沈渔郡,主编.精神病学.第4版.北京:人民卫生出版社.2002:449-453
6.张振馨,魏镜,洪霞,等.北京市城乡痴呆及其主要亚型的患病率.中华神经科杂志,2001,34:199-203
7.陈忠,魏尔清.突触可塑性的机制.中国神经科学杂志,2001,17(3):247-253
8.Maren S,Baudry M.Properties and mechanism of long-term synaptic plasticity in the mammalian brain:relationship to learning and memory.Neurobiol Learn Mem,1995,63(2):12
9.Redaman S.The hippocampus,long-term potentiation and memory.Clin Exp Pharmacol Phychol,1996,23:961
10.章子贵,杜红燕,陆汉新.小鼠的记忆与脑内突触结构参数变化的相关性.心理学报,1995,27(3):317-321
11.Nusakov DA,Davies HA,Harrison E,et al.Ultrastructural synaptic correlate of spatial learning in rat hippocampus.Neuroscience,1997,80(11):69-71
12.盛树力,主编.老年痴呆从分子生物学到临床诊治.北京:科学技术文献出版社.1999:93-124
13.Olson L,Nordberg A,von Holst H,et al.Nerve growth factor affects 11C-nicotine binding,blood flow,EEG,and verbal episodic memory in an Alzheimer patient(case report).J Neural Transm Park Dis Dement Sect,1992,4(1):79-95
14.陈可冀,主编.跨世纪脑科学:老年痴呆发病机理与诊治.北京:北京医科大学中国协和医科大学联合出版社.1998:251
15.Marijn W,Luijpen.Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Self-Efficacy and Mood in Elderly with Mild Cognitive Impairment.Neurorehabil Neural Repair,2004,18(3):166-175
16.丁晓蓉,于建春,于涛,等.“益气调血,扶本培元”针法从气论治老年性痴呆解辩.中医药学刊,2005,23(2):282-284
17.赵纪岚,余曙光,周奇志,等.针刺对老年大鼠及老年小鼠中枢神经递质的影响.成都药大学学报,1999,22(3):30-31
18.石学敏,韩景献,李平,等.针刺对老化痴呆鼠脑兴奋性氨基酸水平影响的实验研究.中国针灸,1998,18(11):689-692
19.王舒,赵俊宏,杨增瑞,等.针刺对SAM-P/8血浆及心肌NO影响的实验研究.针刺研究,1998,23(4):270-272
20.黄诚,陈汉平,秦秀娣,等.针刺抑制老年大鼠脑与垂体细胞因子基因表达.针刺研究,1998,23(1):24-27
21.高尚仁,王米渠主编.书法针刺调治老年痴呆的行为及细胞水平研究.香港大学出版社.香港;2000:42-43
22.张敏,曹珊.调整细胞信号转导功能障碍是针灸治疗阿尔茨海默病的可能靶点.陕西中医学院学报,2004,27(1):37-39
23.曾芳,赵纪岚,周奇志,等.电针对老年性痴呆模型大鼠海马线粒体酶活性的影响.中国老年学杂志,2006,26(3):68-70
24.罗松,余曙光,韩婷,等.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复,2006,10(27):187-189
25.李忠仁主编.实验针灸学(新世纪全国高等中医院校规划教材).北京:中国中医药出版社,2003:327
26.褚芹,于建春,韩景献.针刺对快速老化痴呆模型小白鼠SAMP8认知功能 的改善作用.中国行为医学科学,2005,14(11):964-965.994
27.Jones DG,Devon RM.An ultrastructural study into the effect of pentobarbition on synaptic organization.Brain Res,1978,147:47-63
28.Gulder FH.Increase in postsynaptic density material in optic target neuron of the rat supyachiasmatic nucleus after bilateral enucleation.Neurosci Lett,1980,17:27-32
29.康慧.针灸治疗健忘初探.黑龙江中医药,1988,(3):33
30.裴廷辅,赵邦莲,刘轩,等.电针刺激百会穴对常人血浆环核苷酸含量影响的实验观察.针灸学报,1989,5(2):1
31.周莉,裴廷辅,杜旭,等.针刺百会对记忆影响的实验观察.黑龙江中医药,1992,5(3):41
32.王津存,黄远桂,温晓妮,等.电针穴位刺激对致痫大鼠海马齿状回神经发生及行为学变化影响的实验研究.第四军医大学学报,2006,27(5):441-444
33.闫兵,何利雷,许能贵,等.电针影响血管性痴呆大鼠学习记忆和海马CA3区Gray Ⅰ型突触超微结构的变化.中国临床康复,2006,10(39):42-45
34.易玮,许能贵,汪帼斌,等.电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究.中国中西医结合杂志,2006,26(8):710-714
35.黄龙祥辑校,王雪苔审订.黄帝明堂经辑校.北京:中国医药科技出版社,1988:141
36.祝捷,余曙光,赵纪岚等.针刺“涌泉”穴对老年大鼠血液流变性的影响[J],成都中医药大学学报.1997;20(2):39-40
37.孙上明,余曙光,曾道冰,等.电针涌泉穴对老年大鼠自由基代谢影响的研究.中国自然医学杂志,2002,4(2):80-82
38.李珉,王刚,张卫,等.电针涌泉穴对衰老大鼠p53和bel-2基因表达的影响.中国临床康复,2004,8(9):1788-1789
39.柳刚,杨骏,许冠荪,等.电针“井穴”对血管性痴呆大鼠海马CA1区超微结构的影响.针灸临床杂志,2003,19(12):38-39
40.柳刚,杨骏,许冠荪,等.电针井穴对血管性痴呆大鼠认知功能、神经行为 学及脑血流量的影响.中国中医药科技,2004,11(5):257-258
41.王海军,余曙光.电针对老年性痴呆模型大鼠海马神经元Bcl—2和细胞色素C调节作用的研究.成都中医药大学硕士论文,2005
42.Takeda T.Senescence accelerated mouse(SAM):a biogerontological resource in aging research.Neurobiol Aging,1999,20(2):105-110
43.Chen GH,Wang YJ,Wang XM,et al.Accelerated senescence prone mouse-8shows early onset of deficits in spatial learning and memory in the rADial six-arm water maze.Physiol Behav.2004,82(5):883-890
44.Chen GH,Wang YJ,Qin S,et al.Age-related spatial cognitive impairment is correlated with increase of synaptotagmin 1 in dorsal hippocampus in SAMP8mice.Neurobiol Aging.2007,28(4):611-618
45.Yaguchi T,Nagata T,Mukasa T,et al.Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.Neuroreport.2006,17(1):105-108
46.石学敏,韩景献,刘庆忠,等.快速老化痴呆模型小鼠(SAMP/8)行为学老化特征的增龄性变化观察.实验动物科学与管理,1999,16(4):10-13
47.Kuo H,Ingram DK,Walker LC et al.Similarities in the age related hoppocampal deposition of periodic acids chiff-positive granules in the senescence-accelerated mouse P8 and C57 BL/ 6 mouse strains.Neuroscience,1996,74(3):733-404
48.张月峰,于建春,李谈,等.“益气调血,扶本培元”针法对快速老化小鼠SAMP8海马和颞叶皮质神经元数量及形态的影响.上海针灸杂志,2005,24(9):40-43
49.Randy S,Vijaya R,John EM.Cholinergic deficits in the septal-hippocampal pathway of the SAM-P/8 senescence accelerated mouse.Brain Research,2003,966:150-156
50.Yang S,Zhang HP,Qiao HF et al.Deterioration in synaptic plasticity of cultured hippocampal neurons of senescence-accelerated mouse prone 8.International Congress Series,2004,1260:325-328
51.杉山博.快速老化小鼠(SAM)—作为痴呆动物的可能性.日本《医学之步》,1988,146(9):225-227
52.Hefti F,Dravid A,Hartikka J.Chronic intraventricular injections of NGF elevate hippocampal choline acetyltransferase activity in Adult rats with septo hippocampal lesions.Brain Res,1984,293:305-311
53.Poon HF,Farr SA,Thongboonkerd V et al.Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid:implications for aging and age-related neurodegenerative disorders.Neurochemistry International,2005,46:159-168
54.万选才,等主编.现代神经生物学.北京:北京医科大学,中国协和医科大学联合出版社,1999:520
55.Squire L R,Zola-Morgan S.Memory brain system and behavior.Trends in Neuro Science,1998,11:170
56.成戎川,赵士福,周竹娟,等.老年大鼠空间参考学习和记忆能力改变的研究.中国药业,2006,15(16):10-11
57.松川秀夫,刘公望.刘公望教授对阿尔茨海默型痴呆的针灸治疗经验.天津中医药.2006,23(1):79-81
58.周友龙,韩红艳.针灸治疗阿尔兹海默病的临床研究进展.针灸临床杂志,2006,22(11):50-53
59.罗玳红,唐纯志,赖新生.电针对老年性痴呆模型大鼠学习记忆影响的实验研究.新中医,2003,35(11):77-78
60.李明,吴正治,李耀芳,等.天泰1号对自发阿尔茨海默病鼠海马CA1区分子层突触可塑性的影响:超微结构定量研究.中国临床康复,2005,9(45):182-184
61.胡镜清,赖世隆,王奇,等.补肾益智方阻抑老年性痴呆大鼠海马突触病理性重构的研究.2000,17(2):113-116
62.罗玳红,唐文志,赖新生.电针对老年性痴呆模型大鼠学习记忆影响的实验研究.新中医,2003,35(11):77-78
63.刘雨星,粱繁荣,余曙光,等.电针对穹隆-海马伞损伤老年痴呆大鼠学习记 忆行为影响的实验研究.中国康复医学杂志,2004,19(3):188-190
64.宋玉娟,张力,徐会深,等.电针治疗阿尔茨海默病的实验研究.中医药学报,2005,33(3):39-40
65.Magarious AM,McEwen BS.Stress-induced atrophy of apical dendrites of hippocampal CA3 neurons:comparison of stressors.Neuroscience,1995,69(1):83-88.38
66.Magarious AM,Verdugo JM,McEwen BS.Chronic stress alters synaptic terminal structure in hippocampus.Proc.Natl.Acad.Sci,1997,94:14002-14008
67.章子贵,陆汉新,李振武,等.小鼠记忆保持能力与海马CA3区突触界面结构的相关性.神经科学,1995,2(3):136
68.吴馥梅,杜红燕,章子贵.突触界面曲率及其生理意义.神经解剖学杂志,1994,10(1):89-92
69.赵小贞,王伟,康仲函,等.血管性痴呆大鼠海马突触结构参数的变化.解剖学杂志,2002,25(1):30-34
70.张艳玲,李露斯,可金星,等.血管性痴呆大鼠的记忆行为改变与突触结构参数的关系.第三军医大学学报,2002,24(12):1388-1390
71.张瑞岭,郝伟,刘克菊,等.慢性吗啡处理大鼠伏隔核、海马CA1神经元突触可塑性研究.中国民康医学杂志,2004,16(3):132-134
72.章子贵,杜红燕,姜建明,等.衰老过程中小鼠学习记忆与脑内突触结构参数变化的相关性.神经解剖学杂志,1998,14(2):147-151
73.David C,Chen J.Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizues.J Neurochemistry,2000,74(3):1215-1223
74.王跃春,孙黎明,王子栋,等.损毁大鼠中枢去甲肾上腺素能系统对海马CA3区突触形态的影响.中国病理生理杂志,2004,20(6):994-997
75.Takagi N,Logan R,Teves L,et al.Altered interaction between PSD-95 and the NMDA receptor following transient global ischemia.J Neurochem,2000,74(1):169-178
76.Sheng M.The postsynaptic NMDA-receptor-PSD-95 signaling complex in excitatory synapses of the brain.J Cell Sci,2001,114(7):1251-1252
77.Gardoni F,Schrama LH,Kamal A,et al.Hippocampal synaptic plasticity involves competition between Ca~(2+)/ calmodulin-dependent protein kinase Ⅱand postsynaptic density 95 for binding to the NR2A subunit of the NMDA receptor.Neuroscience,2001,21(5):1501-1509
78.汪帼斌,许能贵,余世锋,等.电针对局灶性脑缺血大鼠缺血区突触结构的影响.中国临床康复,2005,9(5):115-117
79.Biederer T,S a ra Y,Mozhayera M,et al.SynCAM,a synaptic adhesion molecule that drives synapse assembly.Science,2002,297(5586):1525-1531
80.蒲昭霞,赵聪敏,鲁利群.丰富环境对缺氧缺血性脑损伤大鼠海马突触超微结构及突触素表达的影响.第三军医大学学报,2006,28(8):816-818
81.龚石,冯慎远.锌对人鼠学习记忆的影响及其与海马CA_3区和人脑皮质感觉运动区突触界面结构的相关性研究.解剖学杂志,2000,23(1):44
82.原淑娟,张志雄,吴定宗.D-半乳糖对大鼠海马氨基酸含量及海马CA_1区突触结构参数的影响.中国老年学杂志,2002,22(6):500-502
1.韩太真.突触可塑性与长时程增强现象的研究进展.西安交通大学学报(医学版),2005,26(4):305-308
2.韩太真,吴馥梅.学习与记忆的神经生物学.北京:北京医科大学中国协和医科大学联合出版社,1998;162-177
3.Johansson BB.Brain plasticity and Stroke Rehabilitation.The Willis lecture,Stroke 2000,31(1):223-230
4.Rossini PM,Calautti C,Pauri F,et al.Post-stroke plastic:reorganization in the adult brain.Lancet Neurol,2003,2(8):493-502
5.梅镇彤.学习和记忆的神经生物学.上海:上海科技教育出版社,1997:37
6.刘传玉,梅元武.脑缺血与脑的可塑性.国外医学神经病学神经外科学分册,2004,31(6):522-525
7.汪帼斌,许能贵,佘世锋,等.电针对局灶性脑缺血大鼠缺血区突触结构的影响.中国临床康复,2005,9(5):115-117
8.张雪朝,孙国杰.针刺对缺血再灌注大鼠海马脑源性神经营养因子mRNA 的影响.中国神经免疫学和神经病学杂志,2004,11(2):98-101
9.许能贵,汪帼斌,余世锋,等.电针对不同时间段局灶性脑缺血大鼠缺血区皮层BDNF表达的影响.中医药通报·针灸研究,2004,3(4):33-35
10.骆仲达,骆仲逵,许能贵,等.电针对局灶性脑缺血大鼠神经细胞凋亡及神经生长因子的影响.中国临床康复,2004,8(7):1382-1383
11.许能贵,汪帼斌,易玮,等.电针对不同时间段局灶性脑缺血大鼠缺血区皮层突触素P38和GAP—43表达的影响.针刺研究,2004,29(2):85-89
12.易玮,许能贵,汪帼斌,等.电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究.中国中西医结合杂志,2006,26(8):710-714
13.陈英辉,黄显奋.电针对MCAO大鼠脑内GAP-43和突触囊泡蛋白表达的影响.中国针灸,2002,22(6):413-416
14.裴海涛,邹壮丽.头穴针刺对局灶性脑缺血再灌注大鼠脑内TGF-β_((1))mRNA 表达的调节.中国针灸,2003,23(12):739-741
15.刘波,唐强,李静.针刺治疗缺血性脑损伤的实验研究.中国康复理论与实践,2005,11(7):514-515
16.陈加俊,石岩殊,韩雪梅,等.大鼠脑梗死后突触素的变化及针刺的影响.中国老年学杂志,2004,24(4):333-335
17.李常新,黄如训,陈立云,等.电针对大脑中动脉闭塞大鼠脑内神经元特异性烯醇化酶及胶质纤维酸性蛋白表达的影响.中华物理医学与康复杂志,2003,25(12):708-712
18.杨卓欣,于海波,王玲,等.电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响.广州中医药大学学报,2005,22(2):118-121
19.唐勇,陈瑾.针灸治疗帕金森病的临床及实验:5年研究进展.中国临床康复,2004,8(34):7759-7761
20.唐勇,余曙光,陈瑾.电针促进帕金森病模型小鼠黑质致密部突触可塑性的神经细胞黏附机制.中国老年学杂志,2005,25(4):410-412
21.唐勇,余曙光,陈瑾.电针促进帕金森小鼠黑质致密部突触形态可塑性的研究.成都中医药大学学报,2005,28(1):29-32
22.唐勇,余曙光,陈瑾.电针对帕金森小鼠黑质致密部脑源性神经营养因子表达的影响.针刺研究,2006,31(1):38-42
23.陈忠,魏尔清.突触可塑性的机制.中国神经科学杂志,2001,17(3):247-253
24.Maren S,Baudry M.Properties and mechanism of long-term synaptic plasticity in the mammalian brain:relationship to learning and memory.Neurobiol Learn Mem,1995,53(2):12
25.Redaman S.The hippocampus,long—term potentiation and memory.Clin Exp Pharmacol Phychol,1995,23:951
26.刘雨星,梁繁荣,余曙光,等.电针对穹隆一海马伞损伤老年痴呆大鼠学习记忆行为影响的实验研究.中国康复医学杂志,2004,19(3):188-190
27.王援朝,朱丽霞,刘忠武.针刺防治糖尿病性学习记忆障碍.针刺研究,2003,28(1):21-25
28.王富春,时岩.针刺对剥夺性弱视猫视觉系统脑源性神经营养因子的影响.长 春中医学院学报,2003,19(3):72-74
29.陈建国.突触可塑性及其功能.咸宁学院学报(医学版),2004,18(3):153-156
30.胡波,隋建峰.神经胶质细胞调节突触可塑性机制的研究进展.中华神经医学杂志,2005,4(3):306-308
31.郭爱克.从研究脑的发育和可塑性来揭示脑与智力和创造性的关系.生命科学,2006,18(1):15-17
32.郭立达,王捷,夏冰.成体干细胞的可塑性研究.广东医学,2005,26(11):1588-1590
2.张均田.老年痴呆的发病机制及防治药物.医药导报,2002,21(8):469-471
3.何跃.老年性痴呆患病率及神经生化标志物的研究现状.中国临床康复,2005,9(4):143-145
4.盛树力,主编.老年性痴呆的治疗与护理.北京:科学文献出版社.2000:232
5.沈渔郡,主编.精神病学.第4版.北京:人民卫生出版社.2002:449-453
6.张振馨,魏镜,洪霞,等.北京市城乡痴呆及其主要亚型的患病率.中华神经科杂志,2001,34:199-203
7.陈忠,魏尔清.突触可塑性的机制.中国神经科学杂志,2001,17(3):247-253
8.Maren S,Baudry M.Properties and mechanism of long-term synaptic plasticity in the mammalian brain:relationship to learning and memory.Neurobiol Learn Mem,1995,63(2):12
9.Redaman S.The hippocampus,long-term potentiation and memory.Clin Exp Pharmacol Phychol,1996,23:961
10.章子贵,杜红燕,陆汉新.小鼠的记忆与脑内突触结构参数变化的相关性.心理学报,1995,27(3):317-321
11.Nusakov DA,Davies HA,Harrison E,et al.Ultrastructural synaptic correlate of spatial learning in rat hippocampus.Neuroscience,1997,80(11):69-71
12.盛树力,主编.老年痴呆从分子生物学到临床诊治.北京:科学技术文献出版社.1999:93-124
13.Olson L,Nordberg A,von Holst H,et al.Nerve growth factor affects 11C-nicotine binding,blood flow,EEG,and verbal episodic memory in an Alzheimer patient(case report).J Neural Transm Park Dis Dement Sect,1992,4(1):79-95
14.陈可冀,主编.跨世纪脑科学:老年痴呆发病机理与诊治.北京:北京医科大学中国协和医科大学联合出版社.1998:251
15.Marijn W,Luijpen.Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Self-Efficacy and Mood in Elderly with Mild Cognitive Impairment.Neurorehabil Neural Repair,2004,18(3):166-175
16.丁晓蓉,于建春,于涛,等.“益气调血,扶本培元”针法从气论治老年性痴呆解辩.中医药学刊,2005,23(2):282-284
17.赵纪岚,余曙光,周奇志,等.针刺对老年大鼠及老年小鼠中枢神经递质的影响.成都药大学学报,1999,22(3):30-31
18.石学敏,韩景献,李平,等.针刺对老化痴呆鼠脑兴奋性氨基酸水平影响的实验研究.中国针灸,1998,18(11):689-692
19.王舒,赵俊宏,杨增瑞,等.针刺对SAM-P/8血浆及心肌NO影响的实验研究.针刺研究,1998,23(4):270-272
20.黄诚,陈汉平,秦秀娣,等.针刺抑制老年大鼠脑与垂体细胞因子基因表达.针刺研究,1998,23(1):24-27
21.高尚仁,王米渠主编.书法针刺调治老年痴呆的行为及细胞水平研究.香港大学出版社.香港;2000:42-43
22.张敏,曹珊.调整细胞信号转导功能障碍是针灸治疗阿尔茨海默病的可能靶点.陕西中医学院学报,2004,27(1):37-39
23.曾芳,赵纪岚,周奇志,等.电针对老年性痴呆模型大鼠海马线粒体酶活性的影响.中国老年学杂志,2006,26(3):68-70
24.罗松,余曙光,韩婷,等.电针对阿尔茨海默病模型大鼠海马神经元突触形态可塑性的影响机制.中国临床康复,2006,10(27):187-189
25.李忠仁主编.实验针灸学(新世纪全国高等中医院校规划教材).北京:中国中医药出版社,2003:327
26.褚芹,于建春,韩景献.针刺对快速老化痴呆模型小白鼠SAMP8认知功能 的改善作用.中国行为医学科学,2005,14(11):964-965.994
27.Jones DG,Devon RM.An ultrastructural study into the effect of pentobarbition on synaptic organization.Brain Res,1978,147:47-63
28.Gulder FH.Increase in postsynaptic density material in optic target neuron of the rat supyachiasmatic nucleus after bilateral enucleation.Neurosci Lett,1980,17:27-32
29.康慧.针灸治疗健忘初探.黑龙江中医药,1988,(3):33
30.裴廷辅,赵邦莲,刘轩,等.电针刺激百会穴对常人血浆环核苷酸含量影响的实验观察.针灸学报,1989,5(2):1
31.周莉,裴廷辅,杜旭,等.针刺百会对记忆影响的实验观察.黑龙江中医药,1992,5(3):41
32.王津存,黄远桂,温晓妮,等.电针穴位刺激对致痫大鼠海马齿状回神经发生及行为学变化影响的实验研究.第四军医大学学报,2006,27(5):441-444
33.闫兵,何利雷,许能贵,等.电针影响血管性痴呆大鼠学习记忆和海马CA3区Gray Ⅰ型突触超微结构的变化.中国临床康复,2006,10(39):42-45
34.易玮,许能贵,汪帼斌,等.电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究.中国中西医结合杂志,2006,26(8):710-714
35.黄龙祥辑校,王雪苔审订.黄帝明堂经辑校.北京:中国医药科技出版社,1988:141
36.祝捷,余曙光,赵纪岚等.针刺“涌泉”穴对老年大鼠血液流变性的影响[J],成都中医药大学学报.1997;20(2):39-40
37.孙上明,余曙光,曾道冰,等.电针涌泉穴对老年大鼠自由基代谢影响的研究.中国自然医学杂志,2002,4(2):80-82
38.李珉,王刚,张卫,等.电针涌泉穴对衰老大鼠p53和bel-2基因表达的影响.中国临床康复,2004,8(9):1788-1789
39.柳刚,杨骏,许冠荪,等.电针“井穴”对血管性痴呆大鼠海马CA1区超微结构的影响.针灸临床杂志,2003,19(12):38-39
40.柳刚,杨骏,许冠荪,等.电针井穴对血管性痴呆大鼠认知功能、神经行为 学及脑血流量的影响.中国中医药科技,2004,11(5):257-258
41.王海军,余曙光.电针对老年性痴呆模型大鼠海马神经元Bcl—2和细胞色素C调节作用的研究.成都中医药大学硕士论文,2005
42.Takeda T.Senescence accelerated mouse(SAM):a biogerontological resource in aging research.Neurobiol Aging,1999,20(2):105-110
43.Chen GH,Wang YJ,Wang XM,et al.Accelerated senescence prone mouse-8shows early onset of deficits in spatial learning and memory in the rADial six-arm water maze.Physiol Behav.2004,82(5):883-890
44.Chen GH,Wang YJ,Qin S,et al.Age-related spatial cognitive impairment is correlated with increase of synaptotagmin 1 in dorsal hippocampus in SAMP8mice.Neurobiol Aging.2007,28(4):611-618
45.Yaguchi T,Nagata T,Mukasa T,et al.Linoleic acid derivative DCP-LA improves learning impairment in SAMP8.Neuroreport.2006,17(1):105-108
46.石学敏,韩景献,刘庆忠,等.快速老化痴呆模型小鼠(SAMP/8)行为学老化特征的增龄性变化观察.实验动物科学与管理,1999,16(4):10-13
47.Kuo H,Ingram DK,Walker LC et al.Similarities in the age related hoppocampal deposition of periodic acids chiff-positive granules in the senescence-accelerated mouse P8 and C57 BL/ 6 mouse strains.Neuroscience,1996,74(3):733-404
48.张月峰,于建春,李谈,等.“益气调血,扶本培元”针法对快速老化小鼠SAMP8海马和颞叶皮质神经元数量及形态的影响.上海针灸杂志,2005,24(9):40-43
49.Randy S,Vijaya R,John EM.Cholinergic deficits in the septal-hippocampal pathway of the SAM-P/8 senescence accelerated mouse.Brain Research,2003,966:150-156
50.Yang S,Zhang HP,Qiao HF et al.Deterioration in synaptic plasticity of cultured hippocampal neurons of senescence-accelerated mouse prone 8.International Congress Series,2004,1260:325-328
51.杉山博.快速老化小鼠(SAM)—作为痴呆动物的可能性.日本《医学之步》,1988,146(9):225-227
52.Hefti F,Dravid A,Hartikka J.Chronic intraventricular injections of NGF elevate hippocampal choline acetyltransferase activity in Adult rats with septo hippocampal lesions.Brain Res,1984,293:305-311
53.Poon HF,Farr SA,Thongboonkerd V et al.Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid:implications for aging and age-related neurodegenerative disorders.Neurochemistry International,2005,46:159-168
54.万选才,等主编.现代神经生物学.北京:北京医科大学,中国协和医科大学联合出版社,1999:520
55.Squire L R,Zola-Morgan S.Memory brain system and behavior.Trends in Neuro Science,1998,11:170
56.成戎川,赵士福,周竹娟,等.老年大鼠空间参考学习和记忆能力改变的研究.中国药业,2006,15(16):10-11
57.松川秀夫,刘公望.刘公望教授对阿尔茨海默型痴呆的针灸治疗经验.天津中医药.2006,23(1):79-81
58.周友龙,韩红艳.针灸治疗阿尔兹海默病的临床研究进展.针灸临床杂志,2006,22(11):50-53
59.罗玳红,唐纯志,赖新生.电针对老年性痴呆模型大鼠学习记忆影响的实验研究.新中医,2003,35(11):77-78
60.李明,吴正治,李耀芳,等.天泰1号对自发阿尔茨海默病鼠海马CA1区分子层突触可塑性的影响:超微结构定量研究.中国临床康复,2005,9(45):182-184
61.胡镜清,赖世隆,王奇,等.补肾益智方阻抑老年性痴呆大鼠海马突触病理性重构的研究.2000,17(2):113-116
62.罗玳红,唐文志,赖新生.电针对老年性痴呆模型大鼠学习记忆影响的实验研究.新中医,2003,35(11):77-78
63.刘雨星,粱繁荣,余曙光,等.电针对穹隆-海马伞损伤老年痴呆大鼠学习记 忆行为影响的实验研究.中国康复医学杂志,2004,19(3):188-190
64.宋玉娟,张力,徐会深,等.电针治疗阿尔茨海默病的实验研究.中医药学报,2005,33(3):39-40
65.Magarious AM,McEwen BS.Stress-induced atrophy of apical dendrites of hippocampal CA3 neurons:comparison of stressors.Neuroscience,1995,69(1):83-88.38
66.Magarious AM,Verdugo JM,McEwen BS.Chronic stress alters synaptic terminal structure in hippocampus.Proc.Natl.Acad.Sci,1997,94:14002-14008
67.章子贵,陆汉新,李振武,等.小鼠记忆保持能力与海马CA3区突触界面结构的相关性.神经科学,1995,2(3):136
68.吴馥梅,杜红燕,章子贵.突触界面曲率及其生理意义.神经解剖学杂志,1994,10(1):89-92
69.赵小贞,王伟,康仲函,等.血管性痴呆大鼠海马突触结构参数的变化.解剖学杂志,2002,25(1):30-34
70.张艳玲,李露斯,可金星,等.血管性痴呆大鼠的记忆行为改变与突触结构参数的关系.第三军医大学学报,2002,24(12):1388-1390
71.张瑞岭,郝伟,刘克菊,等.慢性吗啡处理大鼠伏隔核、海马CA1神经元突触可塑性研究.中国民康医学杂志,2004,16(3):132-134
72.章子贵,杜红燕,姜建明,等.衰老过程中小鼠学习记忆与脑内突触结构参数变化的相关性.神经解剖学杂志,1998,14(2):147-151
73.David C,Chen J.Involvement of caspase-3-like protease in the mechanism of cell death following focally evoked limbic seizues.J Neurochemistry,2000,74(3):1215-1223
74.王跃春,孙黎明,王子栋,等.损毁大鼠中枢去甲肾上腺素能系统对海马CA3区突触形态的影响.中国病理生理杂志,2004,20(6):994-997
75.Takagi N,Logan R,Teves L,et al.Altered interaction between PSD-95 and the NMDA receptor following transient global ischemia.J Neurochem,2000,74(1):169-178
76.Sheng M.The postsynaptic NMDA-receptor-PSD-95 signaling complex in excitatory synapses of the brain.J Cell Sci,2001,114(7):1251-1252
77.Gardoni F,Schrama LH,Kamal A,et al.Hippocampal synaptic plasticity involves competition between Ca~(2+)/ calmodulin-dependent protein kinase Ⅱand postsynaptic density 95 for binding to the NR2A subunit of the NMDA receptor.Neuroscience,2001,21(5):1501-1509
78.汪帼斌,许能贵,余世锋,等.电针对局灶性脑缺血大鼠缺血区突触结构的影响.中国临床康复,2005,9(5):115-117
79.Biederer T,S a ra Y,Mozhayera M,et al.SynCAM,a synaptic adhesion molecule that drives synapse assembly.Science,2002,297(5586):1525-1531
80.蒲昭霞,赵聪敏,鲁利群.丰富环境对缺氧缺血性脑损伤大鼠海马突触超微结构及突触素表达的影响.第三军医大学学报,2006,28(8):816-818
81.龚石,冯慎远.锌对人鼠学习记忆的影响及其与海马CA_3区和人脑皮质感觉运动区突触界面结构的相关性研究.解剖学杂志,2000,23(1):44
82.原淑娟,张志雄,吴定宗.D-半乳糖对大鼠海马氨基酸含量及海马CA_1区突触结构参数的影响.中国老年学杂志,2002,22(6):500-502
1.韩太真.突触可塑性与长时程增强现象的研究进展.西安交通大学学报(医学版),2005,26(4):305-308
2.韩太真,吴馥梅.学习与记忆的神经生物学.北京:北京医科大学中国协和医科大学联合出版社,1998;162-177
3.Johansson BB.Brain plasticity and Stroke Rehabilitation.The Willis lecture,Stroke 2000,31(1):223-230
4.Rossini PM,Calautti C,Pauri F,et al.Post-stroke plastic:reorganization in the adult brain.Lancet Neurol,2003,2(8):493-502
5.梅镇彤.学习和记忆的神经生物学.上海:上海科技教育出版社,1997:37
6.刘传玉,梅元武.脑缺血与脑的可塑性.国外医学神经病学神经外科学分册,2004,31(6):522-525
7.汪帼斌,许能贵,佘世锋,等.电针对局灶性脑缺血大鼠缺血区突触结构的影响.中国临床康复,2005,9(5):115-117
8.张雪朝,孙国杰.针刺对缺血再灌注大鼠海马脑源性神经营养因子mRNA 的影响.中国神经免疫学和神经病学杂志,2004,11(2):98-101
9.许能贵,汪帼斌,余世锋,等.电针对不同时间段局灶性脑缺血大鼠缺血区皮层BDNF表达的影响.中医药通报·针灸研究,2004,3(4):33-35
10.骆仲达,骆仲逵,许能贵,等.电针对局灶性脑缺血大鼠神经细胞凋亡及神经生长因子的影响.中国临床康复,2004,8(7):1382-1383
11.许能贵,汪帼斌,易玮,等.电针对不同时间段局灶性脑缺血大鼠缺血区皮层突触素P38和GAP—43表达的影响.针刺研究,2004,29(2):85-89
12.易玮,许能贵,汪帼斌,等.电针对局灶性脑缺血大鼠突触可塑性促进作用的实验研究.中国中西医结合杂志,2006,26(8):710-714
13.陈英辉,黄显奋.电针对MCAO大鼠脑内GAP-43和突触囊泡蛋白表达的影响.中国针灸,2002,22(6):413-416
14.裴海涛,邹壮丽.头穴针刺对局灶性脑缺血再灌注大鼠脑内TGF-β_((1))mRNA 表达的调节.中国针灸,2003,23(12):739-741
15.刘波,唐强,李静.针刺治疗缺血性脑损伤的实验研究.中国康复理论与实践,2005,11(7):514-515
16.陈加俊,石岩殊,韩雪梅,等.大鼠脑梗死后突触素的变化及针刺的影响.中国老年学杂志,2004,24(4):333-335
17.李常新,黄如训,陈立云,等.电针对大脑中动脉闭塞大鼠脑内神经元特异性烯醇化酶及胶质纤维酸性蛋白表达的影响.中华物理医学与康复杂志,2003,25(12):708-712
18.杨卓欣,于海波,王玲,等.电针对缺血性脑损伤大鼠海马齿状回突触传递活动的影响.广州中医药大学学报,2005,22(2):118-121
19.唐勇,陈瑾.针灸治疗帕金森病的临床及实验:5年研究进展.中国临床康复,2004,8(34):7759-7761
20.唐勇,余曙光,陈瑾.电针促进帕金森病模型小鼠黑质致密部突触可塑性的神经细胞黏附机制.中国老年学杂志,2005,25(4):410-412
21.唐勇,余曙光,陈瑾.电针促进帕金森小鼠黑质致密部突触形态可塑性的研究.成都中医药大学学报,2005,28(1):29-32
22.唐勇,余曙光,陈瑾.电针对帕金森小鼠黑质致密部脑源性神经营养因子表达的影响.针刺研究,2006,31(1):38-42
23.陈忠,魏尔清.突触可塑性的机制.中国神经科学杂志,2001,17(3):247-253
24.Maren S,Baudry M.Properties and mechanism of long-term synaptic plasticity in the mammalian brain:relationship to learning and memory.Neurobiol Learn Mem,1995,53(2):12
25.Redaman S.The hippocampus,long—term potentiation and memory.Clin Exp Pharmacol Phychol,1995,23:951
26.刘雨星,梁繁荣,余曙光,等.电针对穹隆一海马伞损伤老年痴呆大鼠学习记忆行为影响的实验研究.中国康复医学杂志,2004,19(3):188-190
27.王援朝,朱丽霞,刘忠武.针刺防治糖尿病性学习记忆障碍.针刺研究,2003,28(1):21-25
28.王富春,时岩.针刺对剥夺性弱视猫视觉系统脑源性神经营养因子的影响.长 春中医学院学报,2003,19(3):72-74
29.陈建国.突触可塑性及其功能.咸宁学院学报(医学版),2004,18(3):153-156
30.胡波,隋建峰.神经胶质细胞调节突触可塑性机制的研究进展.中华神经医学杂志,2005,4(3):306-308
31.郭爱克.从研究脑的发育和可塑性来揭示脑与智力和创造性的关系.生命科学,2006,18(1):15-17
32.郭立达,王捷,夏冰.成体干细胞的可塑性研究.广东医学,2005,26(11):1588-1590