Serotonin (5‐HT) regulates neurite outgrowth through 5‐HT1A and 5‐HT7 receptors in cultured hippocampal neurons
Serotonin (5‐HT) regulates neurite outgrowth through 5‐HT1A and 5‐HT7 receptors in cultured hippocampal neurons
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DOI：
10.1002/jnr.23390
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发表时间：
2014-08
影响因子：
4.2
通讯作者：
P. Rojas;D. Neira;M. Muñoz;S. Lavandero;J. Fiedler
中科院分区：
文献类型：
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作者：
P. Rojas;D. Neira;M. Muñoz;S. Lavandero;J. Fiedler
5-羟色胺（5-HT）的产生和5-HT受体（5-HTR）的表达发生在产前发育的早期。最近的证据表明，除了作为神经递质的经典作用外，5-HT还通过调节细胞迁移和神经元细胞结构来调节哺乳动物发育期间的神经元连接。鉴于5-HTR的多样性，研究人员很难澄清每个受体亚型在大脑发育中的具体作用。然而，由G蛋白偶联的5-HT 1AR和5-HT 7 R介导的信号传导与神经元可塑性相关。因此，我们假设5-HT通过5-HT 1AR和5-HT 7 R促进神经突生长。通过在体外用5-HT和5-HT 1AR和5-HT 7 R的特异性拮抗剂（分别为WAY-100635和SB 269970）处理原代培养物2天，评价了5-HT 1AR和5-HT 7 R对大鼠海马神经元形态学的影响。用100 nM 5-HT刺激海马神经元24 h，对初级神经突的数量或长度均无影响。然而，在5 HT 7 R被阻断后，5-HT的加入增加了初级神经突的数量，表明5 HT 7 R可以抑制神经突的发生。相比之下，5-HT诱导继发性神经突生长，1 μM WAY-100635或SB 269970可抑制该作用。这些结果表明，这两种多巴胺能受体参与继发性神经突生长。我们的结论是，5-HT 1AR和5-HT 7 R调节神经元形态在原代海马培养促进继发性神经突起生长。© 2014 Wiley Periodicals，Inc.
Serotonin (5‐HT) production and expression of 5‐HT receptors (5‐HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5‐HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5‐HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G‐protein‐coupled 5‐HT1AR and 5‐HT7R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5‐HT promotes neurite outgrowth through 5‐HT1AR and 5‐HT7R. The involvement of 5‐HT1AR and 5‐HT7R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5‐HT and specific antagonists for 5‐HT1AR and 5‐HT7R (WAY‐100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5‐HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7R was blocked, the addition of 5‐HT increased the number of primary neurites, suggesting that 5HT7R could inhibit neuritogenesis. In contrast, 5‐HT induced secondary neurite outgrowth, an effect inhibited by 1 μM WAY‐100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5‐HT1AR and 5‐HT7R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth. © 2014 Wiley Periodicals, Inc.