{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:57:08Z","timestamp":1791561428843,"version":"4.3.4"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fncel.2022.956609","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T05:27:00Z","timestamp":1658467620000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["MicroRNA Regulation of the Environmental Impact on Adolescent Neurobehavioral Development: A Systematic Review"],"prefix":"10.3389","volume":"16","author":[{"given":"Ana","family":"V\u00e1zquez-\u00c1gredos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"G\u00e1miz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milagros","family":"Gallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.neubiorev.2021.06.033","article-title":"The importance of non-coding RNAs in environmental stress-related developmental brain disorders: a systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections","volume":"128","author":"Arzua","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ncrna5010021","article-title":"microRNA expression profiles in the ventral hippocampus during pubertal development and the impact of peri-pubertal binge alcohol exposure","volume":"5","author":"Asimes","year":"2019","journal-title":"Non-Coding RNA."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ynstr.2020.100271","article-title":"Long-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability","volume":"13","author":"Cattaneo","year":"2020","journal-title":"Neurobiol. Stress"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1111\/acer.14154","article-title":"Mechanisms of Persistent Neurobiological Changes Following Adolescent Alcohol Exposure: NADIA Consortium Findings","volume":"43","author":"Crews","year":"2019","journal-title":"Alcohol: Clin. Exp. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e12791","DOI":"10.1111\/adb.12791","article-title":"DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence","volume":"25","author":"Cuesta","year":"2020","journal-title":"Addict. Bio."},{"key":"B6","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/npp.2017.284","article-title":"Non-Contingent Exposure to Amphetamine in Adolescence Recruits miR-218 to Regulate Dcc Expression in the VTA","volume":"43","author":"Cuesta","year":"2018","journal-title":"Neuropsychopharmacology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1017\/S1461145713001454","article-title":"Prolonged abstinence from developmental cocaine exposure dysregulates BDNF and its signaling network in the medial prefrontal cortex of adult rats","volume":"17","author":"Giannotti","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1097\/FBP.0000000000000326","article-title":"Epigenetic mechanisms associated with addiction-related behavioural effects of nicotine and\/or cocaine: Implication of the endocannabinoid system","volume":"28","author":"Hayase","year":"2017","journal-title":"Behav. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/tp.2014.99","article-title":"Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure","author":"Hollins","year":"2014","journal-title":"Transl. Psychiatry"},{"key":"B10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.bbi.2016.02.021","article-title":"Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure","volume":"56","author":"Hollins","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21186730","article-title":"Circulating MicroRNAs in extracellular vesicles as potential biomarkers of alcohol-induced neuroinflammation in adolescence: gender differences","volume":"21","author":"Ib\u00e1\u00f1ez","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fped.2014.00103","article-title":"Effects of acute prenatal exposure to ethanol on microRNA expression are ameliorated by social enrichment","volume":"2","author":"Ignacio","year":"2014","journal-title":"Front. Pediatr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fnbeh.2021.678102","article-title":"Adolescent stress reduces adult morphine-induced behavioral sensitization in C57BL\/6J mice","volume":"15","author":"Kamens","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pbb.2022.173360","article-title":"Early life stress and substance use disorders: the critical role of adolescent substance use","volume":"215","author":"Kirsch","year":"2022","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1523\/ENEURO.0401-19.2019","article-title":"MicroRNA-137 drives epigenetic reprogramming in the adult amygdala and behavioral changes after adolescent alcohol exposure","volume":"6","author":"Kyzar","year":"2019","journal-title":"ENeuro."},{"key":"B16","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ncrna4020015","article-title":"Functional interplay between Small Non-Coding RNAs and RNA modification in the Brain","volume":"15","author":"Leighton","year":"2018","journal-title":"Non-Coding RNA"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/5249893","article-title":"Dynamic alterations of miR-34c expression in the hypothalamus of male rats after early adolescent traumatic stress","volume":"2016","author":"Li","year":"2016","journal-title":"Neural Plast."},{"key":"B19","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/dev.21558","article-title":"Early adolescent stress-induced changes in prefrontal cortex miRNA-135a and hippocampal miRNA-16 in male rats","volume":"59","author":"Liu","year":"2016","journal-title":"Dev. Psychol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0124931","article-title":"Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model","volume":"5","author":"Marjonen","year":"2015","journal-title":"PLoS ONE."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep37814","article-title":"Environmental intervention as a therapy for adverse programming by ancestral stress","volume":"6","author":"McCreary","year":"2016","journal-title":"Sci. Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.semcdb.2021.04.011","article-title":"MicroRNA regulation of prefrontal cortex development and psychiatric risk in adolescence","volume":"118","author":"Morgunova","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1007\/s13311-021-01140-4","article-title":"Crosstalk among NLRP3 inflammasome, ETBR signaling, and miRNAs in stress-induced depression-like behavior: a modulatory role for SGLT2 inhibitors","volume":"18","author":"Muhammad","year":"2021","journal-title":"Neurotherapeutics."},{"key":"B24","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.neubiorev.2016.07.013","article-title":"Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?","volume":"70","author":"Mychasiuk","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"The BMJ."},{"key":"B26","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/bpa.12896","article-title":"Role of mTOR-regulated autophagy in spine pruning defects and memory impairments induced by binge-like ethanol treatment in adolescent mice","volume":"31","author":"Pascual","year":"2021","journal-title":"Brain Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0083166","article-title":"Long-term effects of peripubertal binge EtOH exposure on hippocampal microRNA expression in the rat","volume":"8","author":"Prins","year":"2014","journal-title":"PLoS ONE."},{"key":"B28","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.neubiorev.2016.06.008","article-title":"MicroRNAs and the adolescent brain: filling the knowledge gap","volume":"70","author":"Rao","year":"2017","journal-title":"Physiol. Behav."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2021.174148","article-title":"Time-dependent changes in striatal monoamine levels and gene expression following single and repeated amphetamine administration in rats","volume":"904","author":"Sequeira-Cordero","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/j.dcn.2011.08.001","article-title":"Rewards, aversions and affect in adolescence: Emerging convergences across laboratory animal and human data","volume":"1","author":"Spear","year":"2011","journal-title":"Dev. Cogn. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0149-7634(00)00014-2","article-title":"The adolescent brain and age-related behavioral manifestations","volume":"24","author":"Spear","year":"2000","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1016\/j.jadohealth.2012.05.006","article-title":"Adolescent neurodevelopment","volume":"52","author":"Spear","year":"2013","journal-title":"J. Adolesc. Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cells11020261","article-title":"Age-dependent and pathway-specific bimodal action of nicotine on synaptic plasticity in the hippocampus of mice lacking the miR-132\/212 genes","volume":"11","author":"Stojanovic","year":"2022","journal-title":"Cells."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0097955","article-title":"Identification of developmentally regulated PCP-responsive non-coding RNA, prt6, in the rat thalamus","volume":"9","author":"Takebayashi","year":"2014","journal-title":"PLoS ONE."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/cells10102679","article-title":"MicroRNAs in the onset of Schizophrenia","volume":"10","author":"Thomas","year":"2021","journal-title":"Cells."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biopsych.2020.10.015","article-title":"miR-218 in adolescence predicts and mediates vulnerability to stress","volume":"89","author":"Torres-Berr\u00edo","year":"2021","journal-title":"Biol. Psychiatry."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1111\/j.1530-0277.2006.00220.x","article-title":"Ontogeny of acute tolerance to ethanol-induced social inhibition in sprague\u2013dawley rats","volume":"30","author":"Varlinskaya","year":"2006","journal-title":"Alcohol: Clin. Exp. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1007\/s00213-016-4373-z","article-title":"Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB\/c mice: the role of cortical BDNF, microRNA-212, and MeCP2","volume":"233","author":"Viola","year":"2016","journal-title":"Psychopharmacology."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0099855","article-title":"Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS ONE."},{"key":"B40","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jpsychires.2017.08.010","article-title":"FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats","volume":"95","author":"Xu","year":"2017","journal-title":"J. Psychiatr. Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.psyneuen.2018.11.008","article-title":"Short- and long-term alterations of FKBP5-GR and specific microRNAs in the prefrontal cortex and hippocampus of male rats induced by adolescent stress contribute to depression susceptibility","volume":"101","author":"Xu","year":"2019","journal-title":"Psychoneuroendocrinology."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41398-021-01220-1","article-title":"Pre-reproductive stress in adolescent female rats alters oocyte microRNA expression and offspring phenotypes: pharmacological interventions and putative mechanisms","volume":"11","author":"Zaidan","year":"2021","journal-title":"Transl. Psychiatry."},{"key":"B43","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s12035-016-0365-6","article-title":"Abnormal expression of MicroRNAs induced by chronic unpredictable mild stress in rat hippocampal tissues","volume":"55","author":"Zhou","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s00221-022-06305-x","article-title":"Non-coding RNA in alcohol use disorder by affecting synaptic plasticity","volume":"240","author":"Zhu","year":"2022","journal-title":"Exp. Brain Res."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.956609\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T05:27:03Z","timestamp":1658467623000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2022.956609\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":44,"alternative-id":["10.3389\/fncel.2022.956609"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2022.956609","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"956609"}}