Harkany Tibor, Guzmán Manuel, Galve-Roperh Ismael, Berghuis Paul, Devi Lakshmi A, Mackie Ken
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE-17177, Sweden.
Trends Pharmacol Sci. 2007 Feb;28(2):83-92. doi: 10.1016/j.tips.2006.12.004. Epub 2007 Jan 10.
In the postnatal brain, endocannabinoids acting as retrograde messengers regulate the function of many synapses. By contrast, the understanding of endocannabinoid functions that regulate fundamental developmental processes such as cell proliferation, migration, differentiation and survival during patterning of the CNS is just beginning to unfold. Increasing the knowledge of basic developmental and signaling principles that are controlled by endocannabinoids will provide important insights into the molecular mechanisms that establish functional neuronal circuits in the brain. Moreover, determining the molecular basis of permanent modifications to cellular structure and intercellular communication imposed by cannabis smoking during pregnancy will provide novel therapeutic targets for alleviating pathogenic changes in affected offspring. Here, we summarize recent findings regarding the ontogeny of the endocannabinoid system in neurons that sculpt the temporal and spatial diversity of cellular functions during CNS development.
在出生后的大脑中,作为逆行信使的内源性大麻素调节着许多突触的功能。相比之下,对于内源性大麻素在中枢神经系统形成过程中调节细胞增殖、迁移、分化和存活等基本发育过程的功能的理解才刚刚开始。增加对内源性大麻素所控制的基本发育和信号传导原理的了解,将为大脑中建立功能性神经元回路的分子机制提供重要见解。此外,确定孕期吸食大麻对细胞结构和细胞间通讯造成的永久性改变的分子基础,将为减轻受影响后代的致病变化提供新的治疗靶点。在此,我们总结了有关内源性大麻素系统在神经元中的个体发生的最新发现,这些神经元在中枢神经系统发育过程中塑造了细胞功能的时空多样性。