Baranova K A, Rybnikova E A, Mironova V I, Samoilov M O
Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034, St. Petersburg, Russia.
Neurosci Behav Physiol. 2010 Jul;40(6):693-700. doi: 10.1007/s11055-010-9313-5. Epub 2010 Jun 11.
We report here our immunocytochemical studies establishing that the development of a depression-like state in rats following unavoidable stress in a "learned helplessness" model is accompanied by stable activation of the expression of transcription factor NGFI-A in the dorsal hippocampus (field CA1) and the magnocellular paraventricular nucleus of the hypothalamus, along with an early wave of post-stress expression, which died down rapidly, in the ventral hippocampus (the dentate gyrus) and a long period of up to five days of high-level expression in the neocortex. In rats subjected to three sessions of preconditioning consisting of moderate hypobaric hypoxia (360 mmHg, 2 h, with intervals of 24 h), which did not form depression in these circumstances, there were significant changes in the dynamics of immunoreactive protein content in the hippocampus, with a stable increase in expression in the ventral hippocampus and only transient and delayed (by five days) expression in field CA1. In the neocortex (layer II), preconditioning eliminated the effects of stress, preventing prolongation of the first wave of NGFI-A expression to five days, while in the magnocellular hypothalamus, conversely, preconditioning stimulated a second (delayed) wave of the expression of this transcription factor. The pattern of NGFI-A expression in the hippocampus, neocortex, and hypothalamus seen in non-preconditioned rats appears to reflect the pathological reaction to aversive stress, which, rather than adaptation, produced depressive disorders. Post-stress modification of the expression of the product of the early gene NGFI-A in the brain induced by hypoxic preconditioning probably plays an important role in increased tolerance to severe psychoemotional stresses and is an important component of antidepressant mechanisms.
我们在此报告我们的免疫细胞化学研究结果，该研究证实，在“习得性无助”模型中，大鼠在不可避免的应激后出现抑郁样状态的过程中，背侧海马体（CA1区）和下丘脑室旁核大细胞部中转录因子NGFI-A的表达会持续激活，同时腹侧海马体（齿状回）会出现应激后早期表达浪潮，但迅速消退，而新皮层则会出现长达五天的高水平表达。对大鼠进行三次由中度低压缺氧（360 mmHg，2小时，间隔24小时）组成的预处理，在这种情况下不会形成抑郁，海马体中免疫反应性蛋白含量的动态变化有显著改变，腹侧海马体中的表达稳定增加，而CA1区仅出现短暂且延迟（五天）的表达。在新皮层（第二层）中，预处理消除了应激的影响，防止NGFI-A表达的第一波延长至五天，而在室旁核大细胞部中，相反，预处理刺激了该转录因子表达的第二波（延迟）浪潮。在未预处理的大鼠中观察到的海马体、新皮层和下丘脑的NGFI-A表达模式似乎反映了对厌恶应激的病理反应，这种反应产生了抑郁障碍而非适应性反应。缺氧预处理诱导的大脑中早期基因NGFI-A产物表达的应激后修饰可能在提高对严重心理情绪应激的耐受性中起重要作用，并且是抗抑郁机制的重要组成部分。
