1. The Loss of α- and β-Tubulin Proteins Are a Pathological Hallmark of Chronic Alcohol Consumption and Natural Brain Ageing
- Author
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Lucky Legbosi Nwidu, Artur Kocon, Kusum K. Kharbanda, Benito Morentin, Henry K. Gerdes, Daniela Schwendener, Ana-Caroline Raulin, George Allen, Laura Johnson, Luis F. Callado, Fryni Drizou, Rebecca Tarbox, Wajana L Labisso, Jack Enticott, Natalia A. Osna, Wayne G. Carter, Amaia M. Erdozain, John W. Grzeskowiak, and Declan Wayne
- Subjects
0301 basic medicine ,α-tubulin ,use disorders ,in-vivo ,chemistry.chemical_compound ,0302 clinical medicine ,gray-matter ,MAP-tau ,Medicine ,map2 ,Prefrontal cortex ,Cytoskeleton ,prefrontal cortex ,biology ,alcoholism ,white-matter ,General Neuroscience ,3. Good health ,pre-frontal cortex ,MAP-2 ,medicine.anatomical_structure ,Cerebral cortex ,cerebral-cortex ,medicine.medical_specialty ,Article ,alcohol-related brain damage ,lcsh:RC321-571 ,03 medical and health sciences ,Internal medicine ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,acetylation ,neuropathology ,Ethanol ,tubulin ,business.industry ,dependence ,HDAC6 ,Alcohol-related brain damage ,030104 developmental biology ,Endocrinology ,Tubulin ,nervous system ,chemistry ,Ageing ,Acetylation ,ageing ,biology.protein ,β-tubulin ,ethanol ,business ,030217 neurology & neurosurgery - Abstract
Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann&rsquo, 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 &alpha, and &beta, tubulins, and increased levels of acetylated &alpha, 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 &alpha, 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.
- Published
- 2018