Impact of Adolescent Binge Drinking on Brain Development

Understanding Brain Development in Adolescents

Mammalian brains experience significant structural and functional transformations during adolescence. This development is influenced by a complex interaction between genetic factors and environmental conditions. Specific genes must activate at precise times to facilitate maturation. Furthermore, the brain’s responses to environmental stimuli—including hormones essential for sexual maturity, social interactions, emotional experiences, and lifestyle choices such as exercise and nutrition—play a crucial role in gene expression and brain development.

The Role of Epigenetics in Brain Maturation

Genes are not static; they can be activated or deactivated based on environmental factors. A group of proteins known as epigenetic modifiers can influence gene activity without altering the underlying genetic code. This epigenetic regulation is vital for brain development, as it synthesizes social, hormonal, environmental, and genetic signals into an effective maturation process.

Research on Alcohol Exposure During Adolescence

U.S. researchers aimed to investigate the changes in brain chemistry resulting from adolescent alcohol exposure and how these changes influence adult behaviors. In their study, male adolescent rats, 28 days old, received abdominal injections of ethanol (2g/kg) or saline every two days until they had received eight injections, continuing until they reached adulthood. The findings revealed an increase in microRNA-137, a molecule linked to brain function regulation and psychiatric conditions, in the brains of the adult rats exposed to alcohol.

Pathway Analysis and Gene Regulation

Subsequent computational analyses identified that five out of the top ten pathways regulated by microRNA-137 involve a protein known as Lysine-specific demethylase-1 (LSD). As an epigenetic modifier, LSD activates the brain-derived neurotrophic factor (BDNF) gene, which is crucial for neuronal differentiation and function. The study demonstrated that adult rats exposed to alcohol exhibited reduced LSD gene expression and fewer proteins associated with the BDNF gene.

Reversing Alcohol-Induced Brain Damage

Researchers explored whether they could restore the brain chemistry of the affected rats. They applied a treatment using an antagomir, a molecule designed to inhibit the functioning of microRNA-137. The results indicated that administering the antagomir successfully reversed the impact of microRNA-137 on LSD and BDNF gene expression. Treated rats showed a temporary reduction in alcohol consumption; however, once the antagomir treatment ceased, the rats reverted to their previous alcohol consumption behaviors.

Considerations and Limitations

It is essential to recognize that the study exclusively involved male rats, which limits the applicability of the findings to female brains, as their development differs significantly, especially during adolescence. Additionally, behavioral outcomes can vary among different rat strains, complicating the potential to generalize these results to other animal models and humans. The authors of the study acknowledged the antagomir’s potential as a therapeutic approach but also highlighted the numerous challenges that must be addressed in future research.

References

Mychasiuk R & Metz GA. Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models? Neuroscience & Biobehavioral Reviews 70, 189-197 (2016). https://doi.org/10.1016/j.neubiorev.2016.07.013

Spear LP. Effects of adolescent alcohol consumption on the brain and behaviour. Nature Reviews Neuroscience 19, 197 (2018). https://doi.org/10.1038/nrn.2018.103

Mahmoudi E & Cairns M. MiR-137: An important player in neural development and neoplastic transformation. Molecular Psychiatry 22, 44 (2017). https://doi.org/10.1038/mp.2016.1504

Kyzar EJ, Bohnsack JP, Zhang H & Pandey SC. MicroRNA-137 drives epigenetic reprogramming in the adult amygdala and behavioral changes after adolescent alcohol exposure. eNeuro (2019). https://doi.org/10.1523/ENEURO.0401-19.2019