抑郁症的病理生理学基础及动物模型研究进展

doi:10.3969/j.issn.2095-1396.2017.04.002

摘要/Abstract

摘要： 抑郁症是严重威胁人类健康的精神情感性障碍。迄今为止，抑郁症的病因与发病机制尚不明确。该文从抑郁症的病理生理学因素及常用抑郁症动物模型的角度进行综述。通过多种动物模型对药物进行评价，不仅全方位对抗抑郁药物活性筛选进行确认，也能从多个角度对药物的药效机制进行探究，进一步阐释抑郁症的可能病理生理学机制，为抑郁症的治疗和抗抑郁新药评价提供借鉴。

关键词: 抑郁症, 病理生理学, 动物模型

Abstract: Depression is a common recurrent psychiatric disorder，which has severely affected quality of human life. So far，the pathogenesis of depression is still unknown and awaits clarification. This paper is a summary of the pathophysiology and animal models of depression，and provides reference for the treatment of depression and the evaluation of antidepressant drugs.

Key words: depression, pathophysiology, animal model

中图分类号:

R964

张阔，杨静玉，吴春福. 抑郁症的病理生理学基础及动物模型研究进展[J]. 神经药理学报, 2017, 7(4): 8-16.

ZHANG Kuo，YANG Jing-yu，WU Chun-fu. Progress on Pathophysiology and Animal Models of Depression[J]. Acta Neuropharmacologica, 2017, 7(4): 8-16.

参考文献

[1] 何海然, 薛占霞. 抑郁症相关发病机制的研究进展[J]. 神经药理学报, 2016, 6(2):20-25.

[2] Ferrari F, Villa R F. The neurobiology of depression: an integrated overview from biological theories to clinical evidence[J]. Molecular Neurobiology, 2016. 54(7):1-19.

[3] 董栋, 王蕊. 抑郁症相关受体、细胞因子及信号通路的研究进展[J]. 神经药理学报, 2012, 24(5):24-30.

[4] Siegfried Kasper, Emmanuelle Corruble, Anthony Hale, et al. Antidepressant efficacy of agomelatine versus SSRI/SNRI: results from a pooled analysis of head-to-head studies without a placebo control[J]. Int Clin Psychopharmacol, 2013, 28(1):12-19.

[5] Danielle M Gerhard, Eric S Wohleb, Ronald S Duman. Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity[J]. Drug Discovery Today, 2016, 21(3):454-464.

[6] Kushall Kumar, Sorabh Sharma, Puneet Kumar, et al. Therapeutic potential of GABA(B) receptor ligands in drug addiction, anxiety, depression and other CNS disorders[J]. Pharmacology Biochemistry & Behavior, 2013, 110(8):174-184.

[7] Ian Mahar, Francis Rodriguez Bambico, Naguid Mechawar, et al. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects[J]. Neuroscience & Biobehavioral Reviews, 2014, 38:173-192.

[8] Mario F Juruena. Early-life stress and HPA axis trigger recurrent adulthood depression[J]. Epilepsy & Behavior E & B, 2014, 38:148-159.

[9] Ronald S Duman. Neurobiology of stress, depression, and rapid acting antidepressants: remodeling synaptic connections[J]. Depression & Anxiety, 2014, 31(4):291-6.

[10] Carmine M Pariante, Stafford L Lightman. The HPA axis in major depression: classical theories and new developments[J]. Trends in Neurosciences, 2008, 31(9): 464-468.

[11] Thomas Frodl, Veronica O'Keane. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans[J]. Neurobiology of Disease, 2013, 52(4):24-37.

[12] Mario F Juruena, Anthony J Cleare, Andrew S Papadopoulos, et al. Different responses to dexamethasone and prednisolone in the same depressed patients[J]. Psychopharmacology, 2006, 189(2): 225-235.

[13] Chloe Farrell, Veronica O'Keane. Epigenetics and the glucocorticoid receptor: A review of the implications in depression[J]. Psychiatry Research, 2016, 242:349-356.

[14] Dirk Jan Saaltink, Erno Vreugdenhil. Stress, glucocorticoid receptors, and adult neurogenesis: a balance between excitation and inhibition?[J]. Cellular & Molecular Life Sciences Cmls, 2014, 71(13):2499-515.

[15] Christoph Anacker, Patricia A Zunszain, Livia A Carvalho, et al. The glucocorticoid receptor: pivot of depression and of antidepressant treatment?[J]. Psychoneuroendocrinology, 2011, 36(3):415-25.

[16] Sabine Chourbaji, Miriam A Vogt, Peter Gass. Mice that under- or overexpress glucocorticoid receptors as models for depression or posttraumatic stress disorder[J]. Progress in Brain Research, 2008, 167:65–77.

[17] Jana Haase, Eric Brown. Integrating the monoamine, neurotrophin and cytokine hypotheses of depression--a central role for the serotonin transporter?[J]. Pharmacol Ther, 2015, 147, 1-11

[18] Angelika Eggert, Michael A Grotzer, Naohiko Ikegaki, et al. Expression of neurotrophin receptor TrkA inhibits angiogenesis in neuroblastoma[J]. Medical & Pediatric Oncology, 2015, 35(6):569-572.

[19] Quesseveur G, David D J., Gaillard M C., et al. BDNF overexpression in mouse hippocampal astrocytes promotes local neurogenesis and elicits anxiolytic-like activities[J]. Translational Psychiatry, 2013, 3(4):e253.

[20] Hiroyuki Koike, Kenichi Fukumoto, Michihiko Iijima, et al. Role of BDNF/TrkB signaling in antidepressant-like effects of a group II metabotropic glutamate receptor antagonist in animal models of depression[J]. Behavioural Brain Research, 2013, 238(2):48-52.

[21] Glenda M MacQueen, Stephanie Campbell, Bruce S McEwen. Course of illness, hippocampal function, and hippocampal volume in major depression[J]. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(3): 1387-1392.

[22] Robert M Sapolsky. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders[J]. Archives of General Psychiatry, 2000, 57(10): 925-935.

[23]Bruce S McEwen. Stress and hippocampal plasticity[J]. Annual Review of Neuroscience, 1999, 22: 105-122.

[24]Robert Schloesser, Dennisse Jimenez, Sophie Orvoen, et al. Antidepressant-like effects of electroconvulsive seizures require adult neurogenesis in a neuroendocrine model of depression[J]. Brain Stimulation, 2015, 8(5):862-867.

[25] Luca Santarelli, Michael Saxe, Cornelius Gross, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants[J]. Science, 2003, 301(5634): 805-809

[26]Maes M, Vandoolaeghe E, Ranjan R, et al. Increased serum interleukin-1-receptor-antagonist concentrations in major depression[J]. J Affective Disorders, 1995, 36(1): 29-36

[27] Cheryl A Kassed, Miles Herkenham. NF-κB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety[J]. Behavioural Brain Research, 2004, 154(2): 577-584.

[28] Benrick A, Schéle E, Pinnock S B, et al. Interleukin‐6 gene knockout influences energy balance regulating peptides in the hypothalamic paraventricular and supraoptic nuclei[J]. J Neuroendocrinology, 2009, 21(7): 620-628.

[29] Roger D Porsolt, Guy Anton, Nadine Blavet. Behavioural despair in rats: a new model sensitive to antidepressant treatments [J]. Eur J Pharmacol, 1978, 47(4): 379-391.

[30] Lucien Steru, Raymond Chermat, Bernard Thierry, et al. The tail suspension test: a new method for screening antidepressants in mice [J]. Psychopharmacology, 1985, 85(3): 367-370.

[31]Seligman M E, Beagley G. Learned helplessness in the rat [J]. J. Comp. Physiol. Psychol, 1975, 88(2): 534-541.

[32]Katz R J, Roth K A, Carroll B J. Acute and chronic stress effects on open field activity in the rat: implications for a model of depression [J]. Neurosci Biobehav Rev, 1981, 5 : 247-251.

[33]Willner P, Towell A, Sampson D, et al. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant [J]. Psychopharmacology, 1987, 93(3): 358-364.

[34]Su Guang-yue, Yang Jing-yu, Wang Fang, et al. Antidepressant-like effects of Xiaochaihutang in a rat model of chronic unpredictable mild stress[J]. J Ethnopharmacology, 2014, 152(1):217-26.

[35]Harlow H F, Dodsworth R O, Harlow M K. Total social isolation in monkeys [J]. Proc Natl Acad Sci U S A, 1965, 54(1): 90-97.

[36]Greg Miller. Social neuroscience. Why loneliness is hazardous to your health[J]. Science, 2011, 331(6014), 138-140.

[37]Liesl M Heinrich, Eleonora Gullone. The clinical significance of loneliness: a literature review[J]. Clin Psychol Rev, 2006, 26(6): 695-718.

[38]Ma Jie, Wu Chun-fu, Wang Fang, et al. Neurological mechanism of Xiaochaihutang's antidepressant‐like effects to socially isolated adult rats[J]. J Pharmacy & Pharmacology, 2016, 68(10):1340-1349.

[39] Yong-ku Kim, Kyoung-Sae Na, Aye-Mu Myint, et al. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression[J]. Progress in Neuropsychopharmacology & Biological Psychiatry, 2016, 64:277-284.

[40] Pariante, C.M., Lightman, S.L. The HPA axis in major depression: classical theories and new developments [J]. Trends in neurosciences, 2008, 31 : 464-468.与10重复

[41] Charles B Nemeroff, William Gomes Vale. The neurobiology of depression: inroads to treatment and new drug discovery [J]. J Clinical Psychiatry, 2005, 66: 7, 5-13.

[42] Zhao Yun-an, Ma Ru, Shen Jia, et al. A mouse model of depression induced by repeated corticosterone injections[J]. J European Pharmacology, 2008, 581(1-2):113.

[43] Yi Li-tao, Li Jing, Li Huo-chen, et al. Ethanol extracts from Hemerocallis citrina attenuate the decreases of brain-derived neurotrophic factor, TrkB levels in rat induced by corticosterone administration [J]. J. Ethnopharmacol, 2012, 144 : 328-334.

[44] Zhang Kuo, Pan Xing, Wang Fang, et al. Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression[J]. Scientific Reports, 2016, 6:30951.

[45] Zhang Kuo, Yang Jing-yu, Wang Fang, et al. Antidepressant-like effects of Xiaochaihutang in a neuroendocrine mouse model of anxiety/depression[J]. J Ethnopharmacology, 2016, 194:674-683.

[46] Walter Tornatzky, Klaus A Miczek. Long-term impairment of autonomic circadian rhythms after brief intermittent social stress[J]. Physiology & Behavior, 1993, 53(5):983-993.

[47] Zhang Kuo, Wang Fang, Yang Jing-yu, et al. Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice[J]. J Ethnopharmacology, 2015, 175:48-57.

[48] Su Guang-yue, Yang Jing-yu, Wang Fang, et al. Xiaochaihutang prevents depressive-like behaviour in rodents by enhancing the serotonergic system[J]. J Pharmacy & Pharmacology, 2014, 66(6):823-34.

[49] Catherine Belzung, Paul Willner, Pierre Philippot. Depression: from psychopathology to pathophysiology[J]. Current Opinion in Neurobiology, 2015, 30:24-30.

[50] Bartlomiej Pochwat, Magdalena Sowa-Kucma, Katarzyna Kotarska, et al. Antidepressant-like activity of magnesium in the olfactory bulbectomy model is associated with the AMPA/BDNF pathway[J]. Psychopharmacology, 2015, 232(2):355-367.

[51] Nico Liebenberg, Samia R L Joca, Gregers Wegener. Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression[J]. Acta Neuropsychiatrica, 2015, 27(2):90-96.

[52] Laurent Naudon, Malika EI Yacoubi, Jean-Marie Vaugeois, et al. A chronic treatment with fluoxetine decreases 5-HT?A receptors labeling in mice selected as a genetic model of helplessness[J]. Brain Research, 2002, 936(1):68-75.

[53] Yousef Tizabi, Babur H Bhatti, Kebreten Manaye, et al. Antidepressant-like effects of low ketamine dose is associated with increased hippocampal AMPA/NMDA receptor density ratio in female Wistar–Kyoto rats[J]. Neuroscience, 2012, 213(213):72-80.

[54] Dipesh Chaudhury, Jessica J Walsh, Allyson K Friedman, et al. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons[J]. Nature, 2013, 493(7433):532-6.

[55] Kay M Tye, Julie J Mirzabekov, Melissa R Warden, et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour[J]. Nature, 2013, 493(7433):537.