抑郁症的动物模型.ppt

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 mice Conventional transgenic mice Conditional gene-targeting methods Antisense targeting 5 5-HT1AHT1A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 5-HT1BHT1B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 DADA-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 2A2A-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 2C2C-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 2C2C-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 ILIL-6 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 5-HT1AHT1A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 Gr nli a,.,Robert Murison b,d,Bj rn Bjorvatn c,d,Eli S rensen a,Chiara M.Portas a,Reidun Ursin a,d，Chronic mild stress affects sucrose intake and sleep in rats，Behavioural Brain Research 150(2004)139147 2John F.Cryan,Daniel Hoyer,and Athina Markou，Withdrawal from Chronic Amphetamine Induces Depressive-Like Behavioral Effects in Rodents，BIOL PSYCHIATRY 2003;54:4958 3Andrew 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)253262 4.Vijayakumar Mavanjia,b,Subimal Dattaa,*，Clomipramine treatment in neonatal rats alters the brain acetylcholinesterase activity in adulthood，Neuroscience Letters 330(2002)119121 5.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_/392 6.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)811 825 7.Alexandre Urani,Sabine Chourbaji,Fritz A.Henn,Peter Gass*，Modeling depression with transgenic mice:the neurotrophin hypothesis revisited，Clinical Neuroscience Research 3(2003)263269 8Marianne B.Mu ller*,Martin E.Keck，Genetically engineered mice for studies of stress-related clinical conditions，Journal of Psychiatric Research 36(2002)5376 9Eric 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;52:503528 10Overmier 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)245251 12Katz RJ,Schmaltz K.Dopaminergic involvement in attention.A novel animal model.Prog Neuropsychopharmacol 1980;4:58590.Psychopharmacology 13Willner 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),2003 16.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 Pathophysiology 2001,17(9):916-919 18.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 2002 19.郭建友，