抑郁症的动物模型.pptx

抑郁症研究的动物模型抑郁症研究的动物模型基础基础01级级 陈瑶瑶陈瑶瑶I am depressed.Me too.Why we need animal models?The sorts of animal models.The future development of animal models.The uses of animal models Antidepressants screening.Mechanism studying神经生化功能改变模型神经生化功能改变模型应激模型应激模型 条件性饲养模型条件性饲养模型 基因工程动物模型基因工程动物模型 获得性无助模型获得性无助模型 (learned helpless)慢性温和应激模型慢性温和应激模型 (chronic mild stress)行为绝望模型行为绝望模型 (behavioral despair)Gene-engineering miceConventional transgenic miceConditional gene-targeting methodsAntisense targeting5-HT1A5-HT1A受体敲除受体敲除抗抑郁表型抗抑郁表型糖皮质激素受体基因损伤糖皮质激素受体基因损伤抗抑郁表型，焦虑相关的抗抑郁表型，焦虑相关的行为减少行为减少(有待进一步确定有待进一步确定)5-HT1B5-HT1B受体敲除受体敲除拮抗抗抑郁表型，拮抗抗抑郁表型，对对SSRISSRI类抗抑郁药类抗抑郁药敏感性增加敏感性增加谷氨酸脱羧酶基因敲除谷氨酸脱羧酶基因敲除抗抑郁表型抗抑郁表型DA-DA-羟化酶基因敲除羟化酶基因敲除拮抗抗抑郁表型拮抗抗抑郁表型神经细胞黏附分子基因敲神经细胞黏附分子基因敲除除抗抑郁表型抗抑郁表型2A-2A-肾上腺素能受体肾上腺素能受体基因敲除基因敲除抑郁表型，并拮抗抑郁表型，并拮抗抗抑郁表型抗抑郁表型TNFTNF基因敲除基因敲除抗抑郁表型抗抑郁表型2C-2C-肾上腺素能受体肾上腺素能受体基因敲除基因敲除抗抑郁表型抗抑郁表型血管紧张素基因敲除血管紧张素基因敲除抗抑郁表型抗抑郁表型2C-2C-肾上腺素能受体肾上腺素能受体基因过表达基因过表达抑郁表型抑郁表型腺苷受体基因敲除腺苷受体基因敲除抗抑郁表型抗抑郁表型NENE转运子基因敲除转运子基因敲除抗抑郁表型抗抑郁表型速激肽速激肽NK1NK1受体基因敲除受体基因敲除抗抑郁表型抗抑郁表型单胺氧化酶单胺氧化酶A A基因敲除基因敲除抗抑郁表型抗抑郁表型IL-6IL-6基因敲除基因敲除拮抗抗抑郁表型拮抗抗抑郁表型单胺氧化酶单胺氧化酶B B基因敲除基因敲除抗抑郁表型抗抑郁表型多巴胺多巴胺D5D5受体基因敲除受体基因敲除抗抑郁表型抗抑郁表型阿片受体基因敲除阿片受体基因敲除抗抑郁表型抗抑郁表型DARPPDARPP基因敲除基因敲除对盐酸氟西汀敏感性降低对盐酸氟西汀敏感性降低阿片受体基因敲除阿片受体基因敲除抑郁表型抑郁表型CREBCREB突变突变抗抑郁表型抗抑郁表型G-G-G-G-蛋白敲除蛋白敲除拮抗抗抑郁表型拮抗抗抑郁表型BDNFBDNF条件性基因敲除条件性基因敲除抗抑郁表型，对电击敏感抗抑郁表型，对电击敏感性降低性降低5-HT1A5-HT1A受体敲除受体敲除抗抑郁表型抗抑郁表型TrkBTrkB基因敲除基因敲除抗抑郁表型，对抗抑郁药抗抑郁表型，对抗抑郁药敏感性降低敏感性降低展望展望 实验动物模型是研究抑郁症必不可实验动物模型是研究抑郁症必不可少的工具。随着基因工程技术的出少的工具。随着基因工程技术的出现，实验模型的可操作性和多样性现，实验模型的可操作性和多样性都大大改善了。虽然转基因技术仍都大大改善了。虽然转基因技术仍存在很多问题，但其仍有着光明的存在很多问题，但其仍有着光明的前景。前景。Reference_1Janne Grnli a,.,Robert Murison b,d,Bjrn Bjorvatn c,d,Eli Srensen a,Chiara M.Portas a,Reidun Ursin a,d，Chronic mild stress affects sucrose intake and sleep in rats，Behavioural Brain Research 150(2004)1391472John F.Cryan,Daniel Hoyer,and Athina Markou，Withdrawal from Chronic Amphetamine Induces Depressive-Like Behavioral Effects in Rodents，BIOL PSYCHIATRY 2003;54:49583Andrew Harkin*,John P.Kelly,Brian E.Leonard，A review of the relevance and validity of olfactory bulbectomy as a model of depression，Clinical Neuroscience Research 3(2003)2532624.Vijayakumar Mavanjia,b,Subimal Dattaa,*，Clomipramine treatment in neonatal rats alters the brain acetylcholinesterase activity in adulthood，Neuroscience Letters 330(2002)1191215.Ruth E.Grahn a,*,S.E.Hammack a,M.J.Will b,K.A.OConnor a,T.Deak c,P.D.Sparks a,L.R.Watkins a,S.F.Maier a,Blockade of alpha1 adrenoreceptors in the dorsal raphe nucleus prevents enhanced conditioned fear and impaired escape performance following uncontrollable stressor exposure in rats,Behavioural Brain Research 134(2002)387_/3926.Peter Gassa,*,Holger M.Reichardtb,Tatyana Strekalovaa,Fritz Henna,Francois Troncheb,Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors:Models for depression and anxiety?Physiology&Behavior 73(2001)811 8257.Alexandre Urani,Sabine Chourbaji,Fritz A.Henn,Peter Gass*，Modeling depression with transgenic mice:the neurotrophin hypothesis revisited，Clinical Neuroscience Research 3(2003)2632698Marianne B.Mu ller*,Martin E.Keck，Genetically engineered mice for studies of stress-related clinical conditions，Journal of Psychiatric Research 36(2002)53769Eric J.Nestler,Elizabeth Gould,Husseini Manji,Maja Bucan,Ronald S.Duman,Howard K.Gershenfeld,Rene Hen,Susan Koester,Israel Lederhendler,Michael J.Meaney,Trevor Robbins,Lois Winsky,and Steve Zalcman,Preclinical Models:Status of Basic Research in Depression,BIOL PSYCHIATRY 2002;52:50352810Overmier JB,Seligman ME.Effects of inescapable shock upon subsequent escape and avoidance responding.J Comp Physiol Psychol 1967;63:2833.neurotransmitter release in an animal model of depression.Neurochem Int 1992;21:2935.11Barbara Vollmayr*,Fritz A.Henn，Stress models of depression，Clinical Neuroscience Research 3(2003)24525112Katz RJ,Schmaltz K.Dopaminergic involvement in attention.A novel animal model.Prog Neuropsychopharmacol 1980;4:58590.Psychopharmacology13Willner P,Towell A,Sampson D,Sophokleous S,Muscat R.Reduction of sucrose preference by chronic unpredictable mild stress and its restoration by a tricyclic antidepressant.Psychopharmacology(Berl)1987;93:35864.14Willner P,Muscat R,Papp M.Chronic mild stress-induced anhedonia:a realistic animal model of depression.Neurosci Biobehav Rev 1992;16:52534.15许晶许晶,李晓秋，慢性应激抑郁模型的建立及其评价，李晓秋，慢性应激抑郁模型的建立及其评价，Chinese Journal of Behavioral Medical Science 12(1),200316.Moreau JL,Scherschlicht R,Jenck F,Martin JR.Chronic mild stress induced anhedonia model of depression;sleep abnormalities and curative effects of electroshock treatment.Behav Pharmacol 1995;6:6827.17吕俊华吕俊华,钟玲，实验性抑郁症动物模型的评价，中国病理生理杂志钟玲，实验性抑郁症动物模型的评价，中国病理生理杂志Chinese Journal of Pathophysiology2001,17(9):916-91918.John F.Cryan,Athina Markou and Irwin Lucki，Assessing antidepressant activity in rodents:recent developments and future needs TRENDS in Pharmacological Sciences Vol.23 No.5 May 200219.郭建友，李昌煜，葛卫红郭建友，李昌煜，葛卫红,抑郁症动物模型研究进展抑郁症动物模型研究进展,中国临床康复第第八卷第中国临床康复第第八卷第10期期感谢：感谢：肖远、陈怡、刘婷婷、王颖、李逸、阎肖远、陈怡、刘婷婷、王颖、李逸、阎焰、平星杰（排名不分先后）焰、平星杰（排名不分先后）感谢她们在本次讨论中的积极参与；感谢她们在本次讨论中的积极参与；感谢王昕老师老师给我们这次机会；感谢王昕老师老师给我们这次机会；感谢在座各位老师和同学给予的耐心。感谢在座各位老师和同学给予的耐心。