Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: pivotal role of pre- and post-synaptic 5-HT1A receptor expression.
Serotonin-prefrontal cortical circuitry in anxiety and depression phenotypes: pivotal role of pre- and post-synaptic 5-HT1A receptor expression.
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DOI：
10.3389/fnbeh.2014.00199
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发表时间：
2014
影响因子：
3
通讯作者：
Luckhart C
中科院分区：
文献类型：
--
作者：
Albert PR;Vahid-Ansari F;Luckhart C
降低的血清素能活性与焦虑和重度抑郁有关，抗抑郁药直接或间接地增加血清素系统的长期活性。5-羟色胺回路的一个关键组成部分是5-HT 1A自身受体，其作为主要的体树突自身受体来负调节5-羟色胺系统的“增益”。此外，5-HT 1A异源受体在前额叶皮层（PFC）、杏仁核和海马体中大量表达，以介导5-羟色胺对恐惧、焦虑、压力和认知的作用。重要的是，在PFC中，5-HT 1A异源受体在至少两个拮抗剂神经元群体上表达：兴奋性锥体神经元和抑制性中间神经元。啮齿动物模型暗示5-HT 1A受体在焦虑和抑郁样表型中具有突触前和突触后5-HT 1A受体的不同作用。在这篇综述中，我们提出了一个模型的马诺宁-PFC电路，整合的证据，从小鼠遗传模型的焦虑和抑郁症，涉及敲除，抑制，过度表达，或突变的5-羟色胺系统的基因，包括5-HT 1A受体。该模型假设，行为表型随着5-羟色胺活性从无（抑郁/攻击性不焦虑）到低（焦虑/抑郁）再到高（焦虑，不抑郁）的增加而变化。我们确定了一组保守的转录因子，包括Deaf 1，Freud-1/CC 2D 1A，Freud-2/CC 2D 1B和糖皮质激素受体，这些转录因子可能会导致抑郁症中5-HT 1A受体的有害区域变化，以及未来的治疗方法如何针对这些机制。需要进一步的研究来专门测试5-HT受体的锥体与神经元间群体的作用和调节，以更好地理解5-羟色胺在焦虑和抑郁中的作用，并设计更有效的靶向治疗方法。
Decreased serotonergic activity has been implicated in anxiety and major depression, and antidepressants directly or indirectly increase the long-term activity of the serotonin system. A key component of serotonin circuitry is the 5-HT1A autoreceptor, which functions as the major somatodendritic autoreceptor to negatively regulate the “gain” of the serotonin system. In addition, 5-HT1A heteroreceptors are abundantly expressed post-synaptically in the prefrontal cortex (PFC), amygdala, and hippocampus to mediate serotonin actions on fear, anxiety, stress, and cognition. Importantly, in the PFC 5-HT1A heteroreceptors are expressed on at least two antagonist neuronal populations: excitatory pyramidal neurons and inhibitory interneurons. Rodent models implicate the 5-HT1A receptor in anxiety- and depression-like phenotypes with distinct roles for pre- and post-synaptic 5-HT1A receptors. In this review, we present a model of serotonin-PFC circuitry that integrates evidence from mouse genetic models of anxiety and depression involving knockout, suppression, over-expression, or mutation of genes of the serotonin system including 5-HT1A receptors. The model postulates that behavioral phenotype shifts as serotonin activity increases from none (depressed/aggressive not anxious) to low (anxious/depressed) to high (anxious, not depressed). We identify a set of conserved transcription factors including Deaf1, Freud-1/CC2D1A, Freud-2/CC2D1B and glucocorticoid receptors that may confer deleterious regional changes in 5-HT1A receptors in depression, and how future treatments could target these mechanisms. Further studies to specifically test the roles and regulation of pyramidal vs. interneuronal populations of 5-HT receptors are needed better understand the role of serotonin in anxiety and depression and to devise more effective targeted therapeutic approaches.
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影响因子：
6.6
作者：
Benedetti, Francesco;Radaelli, Daniele;Smeraldi, Enrico
通讯作者：
Smeraldi, Enrico
DOI：
10.1111/j.1460-9568.2011.07936.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bang SJ;Jensen P;Dymecki SM;Commons KG
通讯作者：
Commons KG
DOI：
10.1073/pnas.1010669107
发表时间：
2010-12-14
影响因子：
11.1
作者：
Chen, Yong-Jun;Zhang, Meng;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming
影响因子：
11
作者：
Bortolozzi, A.;Castane, A.;Artigas, F.
通讯作者：
Artigas, F.
影响因子：
56.9
作者：
Ansorge, MS;Zhou, MM;Gingrich, JA
通讯作者：
Gingrich, JA