Páv M, Kovářů H, Fišerová A, Havrdová E, Lisá V
Clinic of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Physiol Res. 2008;57(2):151-164. doi: 10.33549/physiolres.930990. Epub 2007 May 16.
Depression is a complex disorder related to chronic inflammatory processes, chronic stress changes and a hippocampal response. There is a increasing knowledge about the role of glial cells in nutrient supply to neurons, maintenance of synaptic contacts and tissue homeostasis within the CNS. Glial cells, viewed in the past as passive elements with a limited influence on neuronal function, are becoming recognized as active partners of neurons and are starting to be discussed as a possible therapeutic target. Their role in the pathogenesis of depressive disorders is also being reconsidered. Attention is devoted to studies of the different types of antidepressants and their effects on transmembrane signaling, including levels of alpha subunits of G proteins in C6 glioma cells in vitro as a model of postsynaptic changes in vivo. These models indicate similarities in antidepressant effects on G proteins of brain cells and effector cells of natural immunity, natural killers and granulocytes. Thus, an antidepressant response can exhibit certain common characteristics in functionally different systems which also participate in disease pathogenesis. There are, however, differences in the astrocyte G-protein responses to antidepressant treatment, indicating that antidepressants differ in their effect on glial signalization. Today mainstream approach to neurobiological basis of depressive disorders and other mood illnesses is linked to abnormalities in transmembrane signal transduction via G-protein coupled receptors. Intracellular signalization cascade modulation results in the activation of transcription factors with subsequent increased production of a wide array of products including growth factors and to changes in cellular activity and reactivity.
抑郁症是一种与慢性炎症过程、慢性应激变化及海马体反应相关的复杂疾病。关于神经胶质细胞在为神经元提供营养、维持突触联系以及中枢神经系统内组织稳态方面的作用,人们的认识日益增加。神经胶质细胞过去被视为对神经元功能影响有限的被动成分,如今正被视作神经元的活跃伙伴,并开始被讨论为一个可能的治疗靶点。它们在抑郁症发病机制中的作用也在被重新审视。研究重点在于不同类型抗抑郁药及其对跨膜信号传导的影响,包括以体外C6胶质瘤细胞中G蛋白α亚基水平作为体内突触后变化模型。这些模型表明,抗抑郁药对脑细胞和天然免疫效应细胞(自然杀伤细胞和粒细胞)的G蛋白作用存在相似性。因此,抗抑郁反应在功能不同但也参与疾病发病机制的系统中可能表现出某些共同特征。然而,星形胶质细胞对抗抑郁治疗的G蛋白反应存在差异,这表明不同抗抑郁药对神经胶质细胞信号传导的影响不同。如今,抑郁症及其他情绪疾病神经生物学基础的主流研究方法与通过G蛋白偶联受体的跨膜信号转导异常有关。细胞内信号传导级联调节导致转录因子激活,随后大量产物(包括生长因子)生成增加,并引起细胞活性和反应性的变化。