Vázquez-Ágredos Ana, Gámiz Fernando, Gallo Milagros
Department of Psychobiology, Institute of Neurosciences (CIBM), University of Granada, Granada, Spain.
Front Cell Neurosci. 2022 Jul 22;16:956609. doi: 10.3389/fncel.2022.956609. eCollection 2022.
Adolescence is a late developmental period marked by pronounced reorganization of brain networks in which epigenetic mechanisms play a fundamental role. This brain remodeling is associated with a peculiar behavior characterized by novelty seeking and risky activities such as alcohol and drug abuse, which is associated with increased susceptibility to stress. Hence, adolescence is a vulnerable postnatal period since short- and long-term deleterious effects of alcohol drinking and drug abuse are a serious worldwide public health concern. Among several other consequences, it has been proposed that exposure to stress, alcohol, or other drugs disrupts epigenetic mechanisms mediated by small non-coding microRNAs (miRNAs). During adolescence, this modifies the expression of a variety of genes involved in neurodevelopmental processes such as proliferation, differentiation, synaptogenesis, neural plasticity, and apoptosis. Hence, the effect of miRNAs dysregulation during adolescence might contribute to a long-term impact on brain function. This systematic review focuses on the miRNA expression patterns in the adolescent rodent brain with special interest in the impact of stress and drugs such as amphetamine, cocaine, nicotine, cannabis, and ketamine. The results point to a relevant and complex role of miRNAs in the regulation of the molecular processes involved in adolescent brain development as part of a dynamic epigenetic network sensitive to environmental events with distinctive changes across adolescence. Several miRNAs have been assessed evidencing changing expression profiles during the adolescent transition which are altered by exposure to stress and drug abuse. Since this is an emerging rapidly growing field, updating the present knowledge will contribute to improving our understanding of the epigenetic regulation mechanisms involved in the neurodevelopmental changes responsible for adolescent behavior. It can be expected that increased knowledge of the molecular mechanisms mediating the effect of environmental threats during the adolescent critical developmental period will improve understanding of psychiatric and addictive disorders emerging at this stage.
青春期是一个发育后期阶段，其特征是脑网络发生显著重组，表观遗传机制在其中发挥着根本性作用。这种大脑重塑与一种特殊行为相关，该行为的特点是寻求新奇和进行危险活动，如酗酒和药物滥用，而这又与应激易感性增加有关。因此，青春期是出生后一个易受伤害的时期，因为酗酒和药物滥用的短期和长期有害影响是全球严重的公共卫生问题。在诸多其他后果中，有人提出，暴露于应激、酒精或其他药物会破坏由小非编码微小RNA（miRNA）介导的表观遗传机制。在青春期，这会改变参与神经发育过程（如增殖、分化、突触形成、神经可塑性和细胞凋亡）的多种基因的表达。因此，青春期miRNA失调的影响可能会对脑功能产生长期影响。本系统综述聚焦于青春期啮齿动物大脑中的miRNA表达模式，特别关注应激和诸如苯丙胺、可卡因、尼古丁、大麻和氯胺酮等药物的影响。结果表明，miRNA在调节青春期大脑发育所涉及的分子过程中发挥着相关且复杂的作用，这是一个对环境事件敏感的动态表观遗传网络的一部分，在整个青春期会发生独特的变化。已经评估了几种miRNA，它们在青春期过渡期间表现出表达谱的变化，而暴露于应激和药物滥用会改变这些变化。由于这是一个迅速发展的新兴领域，更新现有知识将有助于增进我们对参与导致青少年行为的神经发育变化的表观遗传调控机制的理解。可以预期，在青少年关键发育时期，对介导环境威胁影响的分子机制的更多了解将有助于增进对这一阶段出现的精神疾病和成瘾性障碍的理解。
