Takeda H, Tsuji M, Matsumiya T
Department of Pharmacology and Intractable Disease Research Center (Division of Drug Research and Development), Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo, 160-8402 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2000 Aug;20(3):83-91.
It is known that the incompetence of stress adaptation mechanisms is a primary factor affecting disorders such as anxiety and depression. Increased clinical evidence indicates that hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and dysfunction of the brain serotonin (5-HT) nervous system are risk factors associated with these disorders. Given the high sensitivity of hippocampal 5-HT responses to glucocorticoids, functional changes in the hippocampal 5-HT nervous system induced by chronic hypercorticism are attracting more attention. Repeated exposure to stress stimuli or chronic administration of corticosterone produces hippocampal 5-HT1A receptor dysfunction as well as an imbalance in mineralocorticoid and glucocorticoid receptors. We recently demonstrated that activation of the 5-HT1A receptors facilitates the adaptive responses to stress stimuli by acting on the HPA axis. These findings suggest that abnormal coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors-5-HT1A receptors in the hippocampus may be one factor disrupting adaptation to stress situations. Moreover, it is shown that activation of the coupling system affects learning and memory processes associated with stress stimuli. These findings suggest that the functional coupling of glucocorticoid-mineralocorticoid/glucocorticoid receptors and serotonergic neurons in the brain may play a significant role in the recognition of stress stimuli and induction of stress adaptation, and dysfunction of this coupling system may be related to the onset of affective disorders.
众所周知,应激适应机制的功能不全是影响焦虑和抑郁等疾病的主要因素。越来越多的临床证据表明,下丘脑-垂体-肾上腺(HPA)轴功能亢进和脑血清素(5-HT)神经系统功能障碍是与这些疾病相关的危险因素。鉴于海马体5-HT对糖皮质激素反应的高敏感性,慢性高皮质醇血症诱导的海马体5-HT神经系统功能变化正受到越来越多的关注。反复暴露于应激刺激或长期给予皮质酮会导致海马体5-HT1A受体功能障碍以及盐皮质激素和糖皮质激素受体失衡。我们最近证明,5-HT1A受体的激活通过作用于HPA轴促进对应激刺激的适应性反应。这些发现表明,海马体中糖皮质激素-盐皮质激素/糖皮质激素受体-5-HT1A受体的异常偶联可能是破坏对应激情况适应的一个因素。此外,研究表明,偶联系统的激活会影响与应激刺激相关的学习和记忆过程。这些发现表明,大脑中糖皮质激素-盐皮质激素/糖皮质激素受体与血清素能神经元的功能偶联可能在应激刺激的识别和应激适应的诱导中起重要作用,而这种偶联系统的功能障碍可能与情感障碍的发病有关。