L-DOPA-Induced Neurogenesis in the Hippocampus Is Mediated Through GPR143, a Distinct Mechanism of Dopamine.
L-DOPA-Induced Neurogenesis in the Hippocampus Is Mediated Through GPR143, a Distinct Mechanism of Dopamine.
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L-DOPA 诱导的海马神经发生是通过 GPR143（多巴胺的一种独特机制）介导的。
DOI：
10.1093/stmcls/sxab013
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Goshima Y.
中科院分区：
文献类型：
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作者：
Kasahara Y;Masukawa D;Kobayashi K;Yamasaki M;Watanabe M;Goshima Y.
神经发生发生在海马体中贯穿一生，并且涉及各种生理脑功能，如记忆编码和情绪调节。L-3，4-二羟基苯丙氨酸（L-DOPA）长期以来被认为是多巴胺的惰性前体。在这里，我们表明，左旋多巴和它的受体，GPR 143，眼白化病1的基因产物，调节神经发生在齿状回（DG）的多巴胺独立的方式。浓度远低于多巴胺的L-DOPA在抑制其转化为多巴胺的情况下促进野生型小鼠神经干细胞和祖细胞的增殖;这种作用在GPR 143基因缺陷（Gpr 143 −/y）小鼠中被消除。在发育和成年期，海马神经发生减少，在成年Gpr 143 −/ymice中观察到抑郁样行为加剧。DG中GPR 143的补充减弱了受损的神经发生和抑郁样行为。我们的研究结果表明，左旋多巴通过GPR 143调节海马神经发生，从而在海马的情绪调节中发挥作用。
Neurogenesis occurs in the hippocampus throughout life and is implicated in various physiological brain functions such as memory encoding and mood regulation. L-3,4-dihydroxyphenylalanine (L-DOPA) has long been believed to be an inert precursor of dopamine. Here, we show that L-DOPA and its receptor, GPR143, the gene product of ocular albinism 1, regulate neurogenesis in the dentate gyrus (DG) in a dopamine-independent manner. L-DOPA at concentrations far lower than that of dopamine promoted proliferation of neural stem and progenitor cells in wild-type mice under the inhibition of its conversion to dopamine; this effect was abolished in GPR143 gene-deficient (Gpr143−/y) mice. Hippocampal neurogenesis decreased during development and adulthood, and exacerbated depression-like behavior was observed in adultGpr143−/ymice. Replenishment of GPR143 in the DG attenuated the impaired neurogenesis and depression-like behavior. Our findings suggest that L-DOPA through GPR143 modulates hippocampal neurogenesis, thereby playing a role in mood regulation in the hippocampus.