Abstract
Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann’s area 9 of the prefrontal cortex (PFC). Brain samples from 44 individuals were divided into equal groups of 11 control, 11 alcoholic, 11 non-alcoholic suicides, and 11 suicide alcoholics matched for age, sex, and post-mortem delay. Tissue from alcoholic cohorts displayed significantly reduced expression of α- and β-tubulins, and increased levels of acetylated α-tubulin. Protein levels of histone deacetylase-6 (HDAC6), and the microtubule-associated proteins MAP-2 and MAP-tau were reduced in alcoholic cohorts, although for MAPs this was not significant. Tubulin gene expressions increased in alcoholic cohorts but not significantly. Brains from rats administered alcohol for 4 weeks also displayed significantly reduced tubulin protein levels and increased α-tubulin acetylation. PFC tissue from control subjects had reduced tubulin protein expression that was most notable from the sixth to the eighth decade of life. Collectively, loss of neuronal tubulin proteins are a hallmark of both chronic alcohol consumption and natural brain ageing. The reduction of cytosolic tubulin proteins could contribute to the brain volumetric losses reported for alcoholic patients and the elderly.
Highlights
Imbibing moderate quantities of alcohol is commonplace within the social culture of many countries
Since the reductions of tubulin protein levels were common to the alcoholic cohorts and not observed with non-alcoholic suicide patients, we suggest that these changes reflect alcohol-induced pathology and not pathology attributed to other psychiatric disorders
In contrast to the tubulin protein expression that declines with ageing, we show that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) levels are relatively stable after age 60
Summary
Imbibing moderate quantities of alcohol is commonplace within the social culture of many countries. Alcohol use disorders are prevalent within many developed countries [1]; with excessive and harmful alcohol usage responsible for approximately 1 in 7 deaths in men (≈14%). Alcohol consumption damages tissues and organs including the brain, the neuro-toxicological properties of alcohol are incompletely understood. Alcoholics experience undesired emotional and behavioral problems [4,5], and are approximately twice as likely to suffer from a major depressive episode compared to those that are not alcohol-dependent [6]. The ability of chronic alcohol abuse to trigger global neuronal cell death has been a topic of debate, with neurotoxicity of alcohol likely cell-type specific, and display brain regional bias [11,12,13,14,15,16]
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