Increased DNA damage after alcohol exposure

I had a good friend in undergrad that refused to drink alcohol because of its negative affects on the brain. More power to ya... but there's nothing I love more than a margarita with my beloved mexican food! Yum! I read an article by Suman et al. that was recently published about DNA damage and loss of repair mechanisms in rat hippocampus after alcohol exposure. Alcohol is a toxic substance to the brain, which leads to structural and functional damage. The hippocampus is found in the brain and plays a role in flexible cognition and complex activities including navigation, decision-making, and social behavior. Research by Rubin et al. suggests that damage to the hippocampus is associated with failure to adapt to social situations. Damage is also linked to medical conditions such as schizophrenia, autism, Alzheimer's disease, and depression. DNA damage occurs through oxidative stress-induced damage resulting in increased double strand break and decreased repair proteins in the hippocampus. The scientists induced binge drinking on rats and observed the effects on the hippocampus. They specifically looked at alcohol-induced oxidative stress using immunofluorescence staining of 4-Hydroxynonenal (4-HNE), which is a chemical found in higher quantities in animal tissues after oxidative stress due to increased activity in the lipid peroxidation chain reaction. DNA damage was also assessed using immunofluorescence staining of gamma-H2AX, which is a protein that recruits DNA repair proteins and can be used as a biomarker for equal parts of double strand breaks. Furthermore, they looked at downregulation of DNA double strand break repair mechanisms using immunoblots and immunohistochemistry 24 hours after a 4 day alcohol binge. Image quantification was performed by measuring staining intensity using the color deconvolution portion of an open source image processing program called ImageJ. They observed more intense staining of 4-HNE and gamma-H2AX cells in the alcohol treated groups in comparison with the control groups, suggestive of oxidative damage and increased double strand breaks. Results of the signaling pathways connected to DNA damage showed decreased levels of proteins after the alcohol binge. The authors suggested that the damage, reduced repair mechanisms, and/or misrepaired DNA may lead to cell cycle arrest, apoptosis, and even senescence. This could adversely affect the structure and function of the hippocampus and neuron formation.

So why is this research beneficial? What are its potential applications?

The location of the hippocampus in the rat (left) and human brain (right).

References:

Suman S, Kumar S, N'Gouemo P, Datta K. Increased DNA double-strand break was associated with downregulation of repair and upregulation of apoptotic factors in rat hippocampus after alcohol exposure. Alcohol 54 (2016) 45-50.

Rubin R D, Watson P D, Duff M C, Cohen N J. The role of the hippocampus in flexible cognition and social behavior. Frontiers in Human Neuroscience (2014) 8:742