Alcoholism pickles the brain by disrupting protein balance

Not only does alcoholism lead to neural atrophy and diminish total brain weight, but it also leads to a dramatic drop in the levels of select proteins in the brain, according to an article published April 3 in PLOS ONE.

Researchers used a variety of methods, including microscopy and mass spectroscopy to study brain damage caused by alcohol consumption in the human brain.

“The production of toxic ethanol metabolites, and their post-translational modification (PTM) and damage of cellular proteins is one of the proposed mechanisms that contribute to neuronal damage,” wrote Amaia M. Erdozain et al.

A total of 20 alcoholics and 20 matched healthy controls had the Brodmann’s area of their prefrontal cortex examined to reveal a number of proteomics anomalies in the alcoholics, especially around the cortical and subcortical neuron nuclei and in subcortical neuronal patterning.

The researchers found a marked decrease in levels of a spectrin cytoskeletal protein as well as tubulins that form a supportive network for brain cells. There was also a significant increase in an enzyme that initiates the reparation of specific tissue damage.

Alcoholics also demonstrated a dip in cellular proteasome activity, which signals the regulation of proteins within the cytoplasm and nucleus.

“Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioral abnormalities attributed to alcoholics,” the researchers wrote.

Similar protein dysfunction was seen at different degrees in the cerebellum, caudate nucleus and hippocampus indicating that these areas are sensitive to excessive alcohol, as well.

“An examination of the molecular abnormalities that arise as a consequence of cumulative ethanol intoxications will assist with an understanding of the development of tissue pathology,” the authors wrote. “In addition, a characterization of ethanol-induced molecular changes may also provide an insight into the molecular adaptations associated with tolerance, dependence, and an alcoholic’s behavioral abnormalities.

This research could one day inform future therapeutics aimed at countering the morbidity and mortality associated with alcoholism.