Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease
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DOI：
10.1016/j.neubiorev.2008.03.006
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发表时间：
2008-09-01
影响因子：
8.2
通讯作者：
Holmes, Andrew
中科院分区：
文献类型：
--
作者：
Holmes, Andrew
5-羟色胺系统与焦虑和抑郁等应激相关疾病的病理生理学和治疗缓解密切相关。急性应激反应和慢性应激适应的5-羟色胺能调制是由许多分子介导的，这些分子控制着5-羟色胺神经元的发育(Pet-1)、合成(色氨酸羟基酶I和2同工酶)、包装(囊泡单胺转运体2)、突触前和突触后受体(5-HT1A、5-HT1B、5-HT2A、5-HT2C、5-HT3A、5-HT4、5-HT5A、5-HT6、5-HT7)、再摄取(5-HT5转运体)和降解(单胺氧化酶A)。越来越多来自临床前啮齿动物模型的证据，特别是转基因小鼠和近交系小鼠，为这些分子的遗传变异如何影响中缝背核、额叶内侧前皮质和杏仁核之间关键神经回路的发育和功能提供了重要的见解。推而广之，这种变异被认为对人类在应激反应和应激相关疾病风险方面的个体差异有重大影响。目前的文章提供了这一快速发展的研究领域的最新情况。爱思唯尔有限公司出版。
The serotonin system is strongly implicated in the pathophysiology and therapeutic alleviation of stress-related disorders such as anxiety and depression. Serotonergic modulation of the acute response to stress and the adaptation to chronic stress is mediated by a myriad of molecules controlling serotonin neuron development (Pet-1), synthesis (tryptophan hydroxylase I and 2 isozymes), packaging (vesicular monoamine transporter 2), actions at presynaptic and postsynaptic receptors (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3A, 5-HT4, 5-HT5A, 5-HT6, 5-HT7), reuptake (serotonin transporter), and degradation (monoamine oxidase A). A growing body of evidence from preclinical rodents models, and especially genetically modified mice and inbred mouse strains, has provided significant insight into how genetic variation in these molecules can affect the development and function of a key neural circuit between the dorsal raphe nucleus, medial prefrontal cortex and amygdala. By extension, such variation is hypothesized to have a major influence on individual differences in the stress response and risk for stress-related disease in humans. The current article provides an update on this rapidly evolving field of research. Published by Elsevier Ltd.