MicroRNA Regulation of the Environmental Impact on Adolescent Neurobehavioral Development: A Systematic Review

Abstract

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.

Keywords: adolescence; alcohol; behavior; brain; drug; epigenetic; microRNA; stress.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart illustrating the search strategy applied to select the publications included in the review.

Figure 2

Ratio of published articles on miRNAs and neurosciences to the total number of articles published over the last 20 years according to the Europe PMC database.

Figure 3

Network data map of the articles' authorship indicating research groups and collaborations. Collaboration between only two groups its shown in the center of the figure. Some representative authors of each research team are highlighted. Point size represents the number of published articles. Colors show the average citations, and lines show clusters based on co-authorship.

Figure 4

Network data map of the articles' citations. Point size represents the number of citations received and colors the publication year. Lines represent the number of co-citations evidencing only three clusters.