Ontogeny and regulation of the serotonin transporter: providing insights into human disorders.
Ontogeny and regulation of the serotonin transporter: providing insights into human disorders.
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DOI：
10.1016/j.pharmthera.2011.03.013
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发表时间：
2011-07
影响因子：
13.5
通讯作者：
Gould, Georgianna G.
中科院分区：
文献类型：
--
作者：
Daws, Lynette C.;Gould, Georgianna G.
关键词：
5-羟色胺（5-hydroxytryptamine，5-HT）是最早被发现在发育中起作用的神经递质之一。药理学和基因敲除研究已经揭示了5-HT在许多过程中的关键作用，包括细胞分裂、神经元迁移、分化和突触发生。大脑中过量的5-HT似乎与大脑发育异常有关，而大脑发育异常又与神经系统疾病有关。环境中5-HT的水平受大量蛋白质的控制，包括多种突触前和突触后5-HT受体、异源受体、酶和转运蛋白。5-HT转运蛋白（SERT，5-HTT）可以说是环境细胞外5-HT的最强大的调节剂。SERT是5-HT的高亲和力摄取机制，并对多巴胺能神经传递的强度和持续时间施加严格控制。其表达水平或功能的扰动与许多疾病有关，其中突出的是精神疾病。本文综述了SERT在胚胎和出生后早期发育到青春期的个体发育的现有信息，沿着影响其表达和功能的因素，在这些关键的发展窗口。我们整合这些知识，强调如何不适当的SERT表达或其失调可能与精神，心血管和胃肠道疾病的病理生理。
Serotonin (5-hydroxytryptamine, 5-HT) was one of the first neurotransmitters for which a role in development was identified. Pharmacological and gene knockout studies have revealed a critical role for 5-HT in numerous processes, including cell division, neuronal migration, differentiation and synaptogenesis. An excess in brain 5-HT appears to be mechanistically linked to abnormal brain development, which in turn is associated with neurological disorders. Ambient levels of 5-HT are controlled by a vast orchestra of proteins, including a multiplicity of pre- and post-synaptic 5-HT receptors, heteroreceptors, enzymes and transporters. The 5-HT transporter (SERT, 5-HTT) is arguably the most powerful regulator of ambient extracellular 5-HT. SERT is the high-affinity uptake mechanism for 5-HT and exerts tight control over the strength and duration of serotonergic neurotransmission. Perturbation of its expression level or function has been implicated in many diseases, prominent among them are psychiatric disorders. This review synthesizes existing information on the ontogeny of SERT during embryonic and early postnatal development though adolescence, along with factors that influence its expression and function during these critical developmental windows. We integrate this knowledge to emphasize how inappropriate SERT expression or its dysregulation may be linked to the pathophysiology of psychiatric, cardiovascular and gastrointestinal diseases.
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DOI：
10.1111/j.1749-6632.1990.tb16893.x
发表时间：
1990-10-15
影响因子：
5.2
作者：
ANDERSON, GM;HORNE, WC;COHEN, DJ
通讯作者：
COHEN, DJ
DOI：
10.1124/jpet.102.047134
发表时间：
2003-06-01
影响因子：
3.5
作者：
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Blakely, RD
DOI：
10.1073/pnas.0800466105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Baganz, Nicole L.;Horton, Rebecca E.;Daws, Lynette C.
通讯作者：
Daws, Lynette C.
影响因子：
11
作者：
Abraham PM;Kuruvilla KP;Mathew J;Malat A;Joy S;Paulose CS
通讯作者：
Paulose CS
DOI：
10.1073/pnas.0403763101
发表时间：
2004-08-17
影响因子：
11.1
作者：
Barr, CS;Newman, TK;Higley, JD
通讯作者：
Higley, JD