Harkany Tibor, Keimpema Erik, Barabás Klaudia, Mulder Jan
Institute of Medical Sciences, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, United Kingdom.
Mol Cell Endocrinol. 2008 Apr 16;286(1-2 Suppl 1):S84-90. doi: 10.1016/j.mce.2008.02.011. Epub 2008 Mar 4.
Endocannabinoids (eCBs) regulate a broad range of physiological functions in the postnatal brain and are implicated in the neuropathogenesis of psychiatric and metabolic diseases. Accumulating evidence indicates that eCB signaling also serves key functions during neurodevelopment; and is inherently involved in the control of neurogenesis, neural progenitor proliferation, lineage segregation, and the migration and phenotypic specification of immature neurons. Recent advances in developmental biology define fundamental eCB-driven cellular mechanisms that also contribute to our understanding of the molecular substrates of prenatal drug, in particular cannabis, actions. Here, we summarize known organizing principles of eCB-signaling systems in the developing telencephalon, and outline the sequence of decision points and underlying signaling pathways upon CB1 cannabinoid receptor activation that contribute to neuronal diversification in the developing brain. Finally, we discuss how these novel principles affect the formation of complex neuronal networks.
内源性大麻素(eCBs)在出生后脑内调节广泛的生理功能,并与精神和代谢疾病的神经发病机制有关。越来越多的证据表明,eCB信号在神经发育过程中也发挥着关键作用;并且本质上参与神经发生、神经祖细胞增殖、谱系分离以及未成熟神经元的迁移和表型特化的控制。发育生物学的最新进展定义了基本的eCB驱动的细胞机制,这也有助于我们理解产前药物,特别是大麻作用的分子基础。在这里,我们总结了发育中的端脑内eCB信号系统的已知组织原则,并概述了CB1大麻素受体激活后有助于发育中脑神经元多样化的决策点序列和潜在信号通路。最后,我们讨论这些新原则如何影响复杂神经元网络的形成。