Ohtani Nobuyo, Goto Tomohide, Waeber Christian, Bhide Pradeep G
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
J Neurosci. 2003 Apr 1;23(7):2840-50. doi: 10.1523/JNEUROSCI.23-07-02840.2003.
Dopamine is a neuromodulator the functions of which in the regulation of complex behaviors such as mood, motivation, and attention are well known. Dopamine appears in the brain early in the embryonic period when none of those behaviors is robust, raising the possibility that dopamine may influence brain development. The effects of dopamine on specific developmental processes such as neurogenesis are not fully characterized. The neostriatum is a dopamine-rich region of the developing and mature brain. If dopamine influenced neurogenesis, the effects would likely be pronounced in the neostriatum. Therefore, we examined whether dopamine influenced neostriatal neurogenesis by influencing the cell cycle of progenitor cells in the lateral ganglionic eminence (LGE), the neuroepithelial precursor of the neostriatum. We show that dopamine arrives in the LGE via the nigrostriatal pathway early in the embryonic period and that neostriatal neurogenesis progresses in a dopamine-rich milieu. Dopamine D1-like receptor activation reduces entry of progenitor cells from the G(1)- to S-phase of the cell cycle, whereas D2-like receptor activation produces the opposite effects by promoting G(1)- to S-phase entry. D1-like effects are prominent in the ventricular zone, and D2-like effects are prominent in the subventricular zone. The overall effects of dopamine on the cell cycle are D1-like effects, most likely because of the preponderance of D1-like binding sites in the embryonic neostriatum. These data reveal a novel developmental role for dopamine and underscore the relevance of dopaminergic signaling in brain development.
多巴胺是一种神经调质，其在调节诸如情绪、动机和注意力等复杂行为中的作用已广为人知。多巴胺在胚胎期早期就出现在大脑中，而此时这些行为均未充分发育，这就增加了多巴胺可能影响大脑发育的可能性。多巴胺对诸如神经发生等特定发育过程的影响尚未完全明确。新纹状体是发育中和成熟大脑中富含多巴胺的区域。如果多巴胺影响神经发生，那么其影响可能在新纹状体中尤为明显。因此，我们研究了多巴胺是否通过影响外侧神经节隆起（LGE）中祖细胞的细胞周期来影响新纹状体神经发生，LGE是新纹状体的神经上皮前体。我们发现多巴胺在胚胎期早期通过黑质纹状体通路到达LGE，并且新纹状体神经发生在富含多巴胺的环境中进行。多巴胺D1样受体激活减少祖细胞从细胞周期的G1期进入S期，而D2样受体激活则通过促进G1期进入S期产生相反的效果。D1样效应在脑室区较为突出，而D2样效应在室下区较为突出。多巴胺对细胞周期的总体效应是D1样效应，这很可能是因为胚胎新纹状体中D1样结合位点占优势。这些数据揭示了多巴胺在发育过程中的新作用，并强调了多巴胺能信号在大脑发育中的相关性。
