抑郁症研究的动物模型 基础01级 陈瑶瑶.

Presentation on theme: "抑郁症研究的动物模型 基础01级 陈瑶瑶."— Presentation transcript:

1 抑郁症研究的动物模型 基础01级 陈瑶瑶

2 I am depressed. Me too.

3 Why we need animal models?
The sorts of animal models. The future development of animal models.

4 The uses of animal models
Antidepressants screening. Mechanism studying

5 神经生化功能改变模型 应激模型 条件性饲养模型 基因工程动物模型

6 获得性无助模型 (learned helpless) 慢性温和应激模型 (chronic mild stress) 行为绝望模型
(behavioral despair)

7 Gene-engineering mice
Conventional transgenic mice Conditional gene-targeting methods Antisense targeting

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12 5-HT1A受体敲除 抗抑郁表型 糖皮质激素受体基因损伤 抗抑郁表型，焦虑相关的行为减少(有待进一步确定) 5-HT1B受体敲除 拮抗抗抑郁表型，对SSRI类抗抑郁药敏感性增加 谷氨酸脱羧酶基因敲除 DA-β-羟化酶基因敲除 拮抗抗抑郁表型 神经细胞黏附分子基因敲除 α2A-肾上腺素能受体基因敲除 抑郁表型，并拮抗抗抑郁表型 TNFα基因敲除 α2C-肾上腺素能受体基因敲除 血管紧张素基因敲除 α2C-肾上腺素能受体基因过表达 抑郁表型 腺苷受体基因敲除 NE转运子基因敲除 速激肽NK1受体基因敲除 单胺氧化酶A基因敲除 IL-6基因敲除 单胺氧化酶B基因敲除 多巴胺D5受体基因敲除 μ阿片受体基因敲除 DARPP基因敲除 对盐酸氟西汀敏感性降低 δ阿片受体基因敲除 CREB突变 Gα-G-蛋白敲除 BDNF条件性基因敲除 抗抑郁表型，对电击敏感性降低 TrkB基因敲除 抗抑郁表型，对抗抑郁药敏感性降低

13 展望 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。虽然转基因技术仍存在很多问题，但其仍有着光明的前景。

14 Reference ___________________________________________________________________________________________ 1．Janne Grønli a,., Robert Murison b,d, Bjørn Bjorvatn c,d, Eli Sørensen a, Chiara M. Portas a, Reidun Ursin a,d ，Chronic mild stress affects sucrose intake and sleep in rats，Behavioural Brain Research 150 (2004) 139–147 2．John F. Cryan, Daniel Hoyer, and Athina Markou，Withdrawal from Chronic Amphetamine Induces Depressive-Like Behavioral Effects in Rodents，BIOL PSYCHIATRY 2003;54:49–58 3．Andrew 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) 253–262 4. Vijayakumar Mavanjia,b, Subimal Dattaa,*，Clomipramine treatment in neonatal rats alters the brain acetylcholinesterase activity in adulthood，Neuroscience Letters 330 (2002) 119–121 5. Ruth E. Grahn a,*, S.E. Hammack a, M.J. Will b, K.A. O’Connor 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) 263–269 8．Marianne B. Mu¨ ller*, Martin E. Keck，Genetically engineered mice for studies of stress-related clinical conditions，Journal of Psychiatric Research 36 (2002) 53–76 9．Eric 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;52:503–528

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10．Overmier JB, Seligman ME. Effects of inescapable shock upon subsequent escape and avoidance responding. J Comp Physiol Psychol 1967;63:28–33. neurotransmitter release in an animal model of depression. Neurochem Int 1992;21:29–35. 11．Barbara Vollmayr*, Fritz A. Henn，Stress models of depression，Clinical Neuroscience Research 3 (2003) 245–251 12．Katz RJ, Schmaltz K. Dopaminergic involvement in attention. A novel animal model. Prog Neuropsychopharmacol 1980;4:585–90. Psychopharmacology 13．Willner 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;93:358–64. 14．Willner P, Muscat R, Papp M. Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 1992;16:525–34. 15．许晶 , 　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: 682–7. 17．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　Chinese Journal of Pathophysiology　2001 ,17(9) : 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，李昌煜，葛卫红, 抑郁症动物模型研究进展, 中国临床康复第第八卷第10期

16 感谢： 肖远、陈怡、刘婷婷、王颖、李逸、阎焰、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。

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