The Loss of α- and β-Tubulin Proteins Are a Pathological Hallmark of Chronic Alcohol Consumption and Natural Brain Ageing

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.

Restorative effect of modified dioscorea pills on the structure of hippocampal neurovascular unit in an animal model of chronic cerebral hypoperfusion

“…MAP-2 is required for dendrite elongation [25]. It was reported that companied with the brain volumetric losses for alcoholic patients and the elderly, microtubule-associated proteins including MAP-2 and MAP-tau were also reduced [26]. Then we can deduce that expression of MAP-2 reflect the rough number of neurons.…”

Tau Is Truncated in Five Regions of the Normal Adult Human Brain

“…In order to gauge if truncation of Tau could be detected in human brains, three different Tau antibodies were used to target epitopes in the middle, the N-terminus, or the C-terminus of the six Tau isoforms present in the human brain ( Figure 1 ). These antibodies have been used in a number of other Tau investigations, e.g., [ 32 , 33 , 34 , 35 , 36 ].…”

“…The results of this study need to be interpreted in the light of the following caveats. Although the three antibodies that were used have been employed in many other published experiments on Tau, e.g., [ 32 , 33 , 34 , 35 , 36 ], we did not independently validate them. Since this was not intended to be a quantitative study, loading controls were not incorporated.…”

Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan

“…Tubulinopathies are characterized by various clinical features and are accompanied by a broad spectrum of malformations of cerebral cortices and subcortical structures, including the corpus callosum, the brainstem, and the basal ganglia [ 41 ]. Loss of α-tubulin and β-tubulin is a hallmark of chronic alcohol consumption and natural brain aging [ 42 ]. Along with these reports, our observations trigger the question of whether accelerated age-dependent loss of these cilia tubulins may contribute to the pathophysiological mechanisms of tubulinopathies.…”