Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone
Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone
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DOI：
10.1038/sj.npp.1300320
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发表时间：
2004-03-01
影响因子：
7.6
通讯作者：
Daszuta, A
中科院分区：
文献类型：
--
作者：
Banasr, M;Hery, M;Daszuta, A
5-羟色胺(5-羟色胺)传递的增加具有深远的抗抑郁作用，并与成人神经发生的增加有关。本研究旨在筛选参与调节齿状回颗粒下层(SGL)和脑室下区(SVZ)细胞增殖的5-羟色胺受体亚型，并确定成年神经发生的长期变化。选择5-HT1A、5-HT1B和5-HT2受体亚型是因为它们在抑郁症中的意义以及它们在这些区域/或邻近这些区域的位置。用不同的激动剂和拮抗剂全身给药，我们发现激活S-HT1A型异源受体后，SGL和SVZ中溴脱氧尿嘧啶核苷标记细胞的数量增加相似(约为对照的50%)，而5-HT2A型和5-HT2C型受体亚型选择性地参与这些区域的细胞增殖调节。激活主要由脉络丛表达的5-HT2C受体使SVZ增加56%，而阻断5-HT2A型受体则使SGL中增殖细胞的数量减少63%。除了5-HT1B自身受体对海马和脑室5-HT1B终末的影响外，5-HT1B异源受体还调节SGL的细胞增殖。这些结果表明，多种受体亚型介导了5-羟色胺对成人脑细胞增殖的部分选择性刺激作用。此外，急性和慢性给予选择性5-HT1A和5-HT2C受体激动剂均可使DG和/或嗅球中新形成的神经元数量持续增加，从而强调了5-羟色胺对成人神经发生的有利作用。
Increase in serotonin (5-HT) transmission has profound antidepressant effects and has been associated with an increase in adult neurogenesis. The present study was aimed at screening the 5-HT receptor subtypes involved in the regulation of cell proliferation in the subgranular layer (SGL) of the dentate gyrus (DG) and the subventricular zone (SVZ) and to determine the long-term changes in adult neurogenesis. The 5-HT1A, 5-HT1B, and 5-HT2 receptor subtypes were chosen for their implication in depression and their location in/ or next to these regions. Using systemic administration of various agonists and antagonists, we show that the activation of S-HT1A heteroreceptors produces similar increases in the number of bromodeoxyuridine-labeled cells in the SGL and the SVZ (about 50% over control), whereas 5-HT2A and 5-HT2C receptor subtypes are selectively involved in the regulation of cell proliferation in each of these regions. The activation of 5-HT2C receptors, largely expressed by the choroid plexus, produces a 56% increase in the SVZ, while blockade of 5-HT2A receptors produces a 63% decrease in the number of proliferating cells in the SGL. In addition to the influence of 5-HT1B autoreceptors on 5-HT terminals in the hippocampus and ventricles, 5-HT1B heteroreceptors also regulate cell proliferation in the SGL. These data indicate that multiple receptor subtypes mediate the potent, partly selective of each neurogenic zone, stimulatory action of 5-HT on adult brain cell proliferation, Furthermore, both acute and chronic administration of selective 5-HT1A and 5-HT2C receptor agonists produce consistent increases in the number of newly formed neurons in the DG and/or olfactory bulb, underscoring the beneficial effects of 5-HT on adult neurogenesis.