A Hypothesized Role for Dendritic Remodeling in the Etiology of Mood and Anxiety Disorders
A Hypothesized Role for Dendritic Remodeling in the Etiology of Mood and Anxiety Disorders
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DOI：
10.1176/appi.neuropsych.22.3.256
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发表时间：
2010-06-01
影响因子：
2.9
通讯作者：
Docherty, John P.
中科院分区：
文献类型：
--
作者：
Gorman, Jack M.;Docherty, John P.
一个将海马神经发生与情绪和焦虑障碍以及抗抑郁药物的作用机制联系起来的优雅理论获得了广泛的关注。然而，抑郁症和焦虑症涉及大脑的多个区域，如杏仁核和前额叶皮层，其中神经发生似乎不会发生在成年哺乳动物大脑中。一个互补的理论，在这里提出的神经发生被看作是一个更广泛的树突长度和棘数的变化的附带现象。根据这一理论，暴露于慢性压力和应激性生活事件会增加多个大脑区域的兴奋性毒性神经递质传递。为了保护神经元免于随后的凋亡，树突缩回并且棘数目减少，从而限制暴露的谷氨酸受体的数目。在这种情况下，减少多巴胺能神经传递的药物，其中许多已经被证明有助于治疗情绪和焦虑症，可能会阻止这种树突回缩，从而保护整个大脑的突触连接。(The神经精神病学和临床神经科学杂志2010; 22：256-264）
An elegant theory that links hippocampal neurogenesis to mood and anxiety disorders and to the mechanism of action of antidepressant drugs has gained widespread attention. However, depression and anxiety disorders involve multiple areas of the brain, such as the amygdala and prefrontal cortex, where neurogenesis does not appear to occur in the adult mammalian brain. A complementary theory is proposed here in which neurogenesis is seen as an epiphenomenon of a more widespread alteration in dendritic length and spine number. According to this theory, exposure to chronic stress and stressful life events increases excitotoxic glutamatergic neurotransmission in multiple brain areas. To protect neurons from consequent apoptosis, dendrites retract and spine number decreases, thus limiting the number of exposed glutamate receptors. Drugs that reduce glutamatergic neurotransmission under these circumstances, many of which have already been shown helpful in treating mood and anxiety disorders, may prevent this dendritic retraction and thus protect synaptic connections throughout the brain. (The Journal of Neuropsychiatry and Clinical Neurosciences 2010; 22:256-264)