McEwen Bruce S
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA.
Metabolism. 2005 May;54(5 Suppl 1):20-3. doi: 10.1016/j.metabol.2005.01.008.
The hippocampal formation expresses high levels of adrenal steroid receptors and is a malleable brain structure that is important for certain types of learning and memory. It is also vulnerable to the effects of stress and trauma. The amygdala is an important target of stress and mediates physiological and behavioral responses associated with fear and strong emotions. The prefrontal cortex plays an important role in working memory and executive function and is also involved in extinction of learning. All 3 regions are targets of stress hormones, and stress is known to precipitate and exacerbate mood disorders. In long-term depressive illness, the hippocampus and prefrontal cortex undergo atrophy, whereas the amygdala is hyperactive in anxiety and mood disorders and may undergo a biphasic change in structure--increasing in size in acute depression and shrinking on long-term depression. In animal models of acute and chronic stress, neurons in the hippocampus and prefrontal cortex respond to repeated stress by showing atrophy that leads to memory impairment, whereas neurons in amygdala show a growth response that leads to increased anxiety and aggression. Yet, these are not necessarily "damaged" and may be treatable with the right medications. The mechanisms that distinguish between protection and damage of brain cells from stress are discussed in this context.
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。它也易受压力和创伤的影响。杏仁核是压力的重要靶点，介导与恐惧和强烈情绪相关的生理和行为反应。前额叶皮质在工作记忆和执行功能中起重要作用，也参与学习消退。这三个区域都是应激激素的靶点，已知压力会引发和加重情绪障碍。在长期抑郁性疾病中，海马和前额叶皮质会发生萎缩，而杏仁核在焦虑和情绪障碍中过度活跃，其结构可能会发生双相变化——在急性抑郁时增大，在长期抑郁时缩小。在急性和慢性应激的动物模型中，海马和前额叶皮质的神经元对反复应激的反应是出现萎缩，导致记忆障碍，而杏仁核的神经元则表现出生长反应，导致焦虑和攻击性增加。然而，这些神经元不一定是“受损”的，可能可以用合适的药物治疗。本文将在这种背景下讨论区分应激对脑细胞的保护和损伤的机制。
