Patel Tushar D, Zhou Feng C
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Medical Science Research Building, Room 508, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Brain Res Dev Brain Res. 2005 Jun 9;157(1):42-57. doi: 10.1016/j.devbrainres.2005.03.006.
Serotonin (5-HT) has long been implicated in a number of neurodevelopmental processes including neuronal cell division, migration, neurite outgrowth, and synapse formation. However, relatively little is known about how these effects are mediated during normal brain development in vivo and the identity of the receptor subtypes involved in mediating these effects. In recent years, a number of pharmacological studies have suggested a role for the serotonin 1A (5HT1A) receptor subtype in mediating the developmental effects of 5-HT in the hippocampus. These studies, however, have been difficult to interpret due to lack of information regarding the expression and distribution of 5HT1A in the developing brain and hippocampus in particular. In the current study, specific anti-5-HT1A antibodies, developed in our laboratory [F.C. Zhou, T.D. Patel, D. Swartz, Y. Xu, M.R. Kelley, Production and characterization of an anti-serotonin 1A receptor antibody which detects functional 5-HT1A binding sites, Brain Res Mol Brain Res, 69 (1999) 186-201], were utilized to map the ontogeny and distribution of the 5HT1A receptor protein in the developing rat hippocampus through embryonic and early postnatal life. This is the first such study of 5-HT1A expression in the developing rat brain. Our findings revealed that expression of the 5HT1A receptor emerges during the initial stages of embryonic hippocampal development. Remarkably, most if not all hippocampal neurons begin to express 5HT1A shortly upon completion of their terminal mitosis. We found that 5HT1A is initially concentrated around the cell bodies and later becomes more sparsely distributed along the dendrites after the neurons have matured. In addition to postmitotic neurons, we have observed that S100 and GFAP positive glia transiently express 5HT1A during early postnatal development of the hippocampus. These findings demonstrate that the 5-HT1A receptor is positioned to mediate developmental effects of serotonin in the hippocampus. Furthermore, the temporal patterns of expression suggest a role for 5-HT1A in postmitotic events such as neuronal migration, neurite outgrowth, and phenotypic differentiation.
血清素（5-羟色胺，5-HT）长期以来一直被认为与许多神经发育过程有关，包括神经元细胞分裂、迁移、神经突生长和突触形成。然而，对于这些效应在体内正常脑发育过程中是如何介导的，以及介导这些效应的受体亚型的身份，我们所知相对较少。近年来，一些药理学研究表明，血清素1A（5HT1A）受体亚型在介导5-HT对海马体的发育效应中发挥作用。然而，由于缺乏关于5HT1A在发育中的大脑尤其是海马体中的表达和分布的信息，这些研究难以解释。在本研究中，我们利用在我们实验室开发的特异性抗5-HT1A抗体[F.C.周，T.D.帕特尔，D.斯沃茨，Y.徐，M.R.凯利，一种检测功能性5-HT1A结合位点的抗血清素1A受体抗体的制备与特性，《脑研究 分子脑研究》，69（1999）186 - 201]，来绘制5HT1A受体蛋白在发育中的大鼠海马体从胚胎期到出生后早期的个体发生和分布图谱。这是首次对发育中的大鼠脑中5-HT1A表达进行此类研究。我们的研究结果表明，5HT1A受体的表达在胚胎海马体发育的初始阶段出现。值得注意的是，大多数（如果不是全部）海马神经元在完成终末有丝分裂后不久就开始表达5HT1A。我们发现，5HT1A最初集中在细胞体周围，在神经元成熟后，沿树突的分布变得更加稀疏。除了有丝分裂后的神经元，我们还观察到，在海马体出生后早期发育过程中，S100和GFAP阳性胶质细胞短暂表达5HT1A。这些发现表明，5-HT1A受体能够介导血清素对海马体的发育效应。此外，表达的时间模式表明5-HT1A在有丝分裂后事件如神经元迁移、神经突生长和表型分化中发挥作用。
