Hoops Daniel, Flores Cecilia
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, QC H4H 1R3, Canada.
Department of Psychiatry, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Boulevard, Montreal, QC H4H 1R3, Canada.
Trends Neurosci. 2017 Dec;40(12):709-719. doi: 10.1016/j.tins.2017.09.004. Epub 2017 Oct 9.
A dramatic maturational process ongoing in adolescence is prefrontal cortex development, including its dopamine innervation. Dopamine axons grow from the striatum to the prefrontal cortex, the only known case of long-distance axon growth during adolescence. This is coordinated by the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer), which in turn controls the intrinsic development of the prefrontal cortex itself. Stimulant drugs in adolescence alter DCC in dopamine neurons and, in turn prefrontal cortex maturation, impacting cognitive abilities. Variations in DCC expression are linked to psychiatric conditions of prefrontal cortex dysfunction, and microRNA regulation of DCC may be key to determining adolescent vulnerability or resilience. Since early interventions are proving to effectively ameliorate disease outcome, the Netrin-1 system is a promising therapeutic target.
青春期正在进行的一个显著成熟过程是前额叶皮质发育，包括其多巴胺神经支配。多巴胺轴突从纹状体生长到前额叶皮质，这是青春期唯一已知的远距离轴突生长情况。这一过程由Netrin-1引导信号受体DCC（结直肠癌缺失基因）协调，而DCC又控制着前额叶皮质自身的内在发育。青春期使用的兴奋性药物会改变多巴胺神经元中的DCC，进而影响前额叶皮质成熟，对认知能力产生影响。DCC表达的变化与前额叶皮质功能障碍的精神疾病有关，DCC的微小RNA调节可能是决定青少年易感性或恢复力的关键。由于早期干预已被证明能有效改善疾病结局，Netrin-1系统是一个有前景的治疗靶点。
