The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

Axon guidance molecules direct growing axons toward their targets, assembling the intricate wiring of the nervous system. One of these molecules, Netrin-1, and its receptor, DCC (deleted in colorectal cancer), has profound effects, in laboratory animals, on the adolescent expansion of mesocorticolimbic pathways, particularly dopamine. Now, a rapidly growing literature suggests that (1) these same alterations could occur in humans, and (2) genetic variants in Netrin-1 and DCC are associated with depression, schizophrenia, and substance use. Together, these findings provide compelling evidence that Netrin-1 and DCC influence mesocorticolimbic-related psychopathological states that emerge during adolescence.

轴突导向分子引导生长的轴突指向其目标，构建神经系统复杂的线路。其中一种分子，轴突导向因子1（Netrin - 1）及其受体结直肠癌缺失蛋白（DCC，deleted in colorectal cancer），在实验动物中对中脑边缘皮质通路（特别是多巴胺相关通路）在青春期的扩展具有深远影响。现在，大量迅速增长的文献表明：（1）人类中可能发生同样的变化；（2）轴突导向因子1和结直肠癌缺失蛋白的基因变异与抑郁症、精神分裂症和物质使用有关。总之，这些发现提供了令人信服的证据，表明轴突导向因子1和结直肠癌缺失蛋白影响在青春期出现的与中脑边缘皮质相关的精神病理状态。