Digging Deep: Effects of adolescent alcohol consumption on the brain

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A latest study has established a connection between teenage alcoholism and brain disorders later in adult life. Healthy brain development throughout childhood and adolescence is important for optimal neurocognitive performance, with even subtle changes in neurodevelopmental trajectories (e.g., changes in brain structural volume, cortical thickness, demyelination) affecting cognitive, emotional, and social functioning.

Alcohol is the most commonly used substance during adolescence. According to the 2013 Monitoring the Future Study, 30% of youth in the United States have used alcohol by eighth grade. These rates more than double during adolescence, with 69% of adolescents reporting alcohol use by the time they graduate high school. The consequences of alcohol use in human adolescents include alterations in attention, verbal learning, visuospatial processing and memory, along with altered development of grey and white matter volumes and disrupted white matter integrity. The functional consequences of adolescent alcohol use emerging from studies of rodent models of adolescence include decreased cognitive flexibility, behavioural inefficiencies and elevations in anxiety, disinhibition, impulsivity and risk-taking. Rodent studies have also showed that adolescent alcohol use can impair neurogenesis, induce neuroinflammation and epigenetic alterations, and lead to the persistence of adolescent-like neurobehavioural phenotypes into adulthood.

There are, however, no changes in the actual DNA sequence, but in the structure of the chromatin – a complex of DNA and proteins – that packs DNA compactly inside the nucleus. In particular, chromatin contains many nucleosomes, which is DNA wrapped around 8 histone proteins, like a thread around a spool. But is there a clear link between alcohol consumption and modifications in the histone protein that suppress ARC protein production? In order to establish a relationship between environment/behaviour and the SARE site, Bohnsack et al. 2022 used CRISPR-dCas9, a tool to used to epigenetic modifications, to modify histone proteins. The dCas9 protein was tethered to P300, a histone protein that promotes production of RNA (RNA is then converted to protein), and targeted at the SARE site. Then, the SARE site was targeted by dCas9 tethered to KRAB, a protein that suppresses RNA copying.

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