McEwen Bruce S, Chattarji Sumantra
Harold and Margaret Milliken Hatch-Laboratory of Neuroendocrinology Rockefeller University, New York, NY 10021, USA.
Eur Neuropsychopharmacol. 2004 Dec;14 Suppl 5:S497-502. doi: 10.1016/j.euroneuro.2004.09.008.
The hippocampal formation, which expresses high levels of adrenal steroid receptors, is a malleable brain structure that is important for certain types of learning and memory. This structure is also vulnerable to the effects of stress hormones which have been reported to be increased in depressed patients, particularly those with severe depression. The amygdala, a structure that plays a critical role in fear learning, is also an important target of anxiety and stress. Certain animal models of depression involve application of repeated stress. Repeated stress promotes behavioral changes that can be associated with these two brain structures such as impairment of hippocampus-dependent memory and enhancement of fear and aggression, which are likely to reflect amygdala function. At a cellular level, opposite responses in the hippocampus and amygdala are observed, namely, shrinkage of dendrites in hippocampus and growth of dendrites in the lateral amygdala, involving in both cases a remodeling of dendrites. Furthermore, stress-induced suppression of neurogenesis has been noted in dentate gyrus. At a molecular level, the effects of repeated stress in the hippocampus involve excitatory amino acids and the induction of the glial form of the glutamate transporter. Chronic treatment with the antidepressant tianeptine may prevent these effects in hippocampus and amygdala.
海马结构表达高水平的肾上腺类固醇受体，是一个具有可塑性的脑结构，对某些类型的学习和记忆很重要。该结构也易受应激激素的影响，据报道，抑郁患者尤其是重度抑郁患者的应激激素会增加。杏仁核在恐惧学习中起关键作用，也是焦虑和应激的重要靶点。某些抑郁症动物模型涉及反复施加应激。反复应激会促使行为发生变化，这些变化可能与这两个脑结构有关，如海马依赖性记忆受损以及恐惧和攻击性增强，这可能反映了杏仁核的功能。在细胞水平上，观察到海马和杏仁核有相反的反应，即海马中树突萎缩，外侧杏仁核中树突生长，两种情况都涉及树突重塑。此外，在齿状回中已注意到应激诱导的神经发生抑制。在分子水平上，反复应激对海马的影响涉及兴奋性氨基酸和谷氨酸转运体胶质形式的诱导。用抗抑郁药噻奈普汀进行慢性治疗可能会预防海马和杏仁核中的这些影响。
