The loss of α- and β-tubulin proteins are a pathological hallmark of chronic alcohol consumption and natural brain ageing

Labisso, Wajana; Raulin, Ana-Caroline; Nwidu, Lucky; Kocon, Artur; Wayne, Declan; Erdozain, Amaia; Morentin, Benito; Schwendener, Daniela; Allen, George; Enticott, Jack; Gerdes, Henry; Johnson, Laura; Grzeskowiak, John; Drizou, Fryni; Tarbox, Rebecca; Osna, Natalia; Kharbanda, Kusum; Callado, Luis; Carter, Wayne

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.

Citation

Labisso, W., Raulin, A.-C., Nwidu, L., Kocon, A., Wayne, D., Erdozain, A., Morentin, B., Schwendener, D., Allen, G., Enticott, J., Gerdes, H., Johnson, L., Grzeskowiak, J., Drizou, F., Tarbox, R., Osna, N., Kharbanda, K., Callado, L., & Carter, W. (2018). The loss of α- and β-tubulin proteins are a pathological hallmark of chronic alcohol consumption and natural brain ageing. Brain Sciences, 8(9), Article 175. https://doi.org/10.3390/brainsci8090175

• Journal Article Type: Article
• Acceptance Date: Sep 2, 2018
• Online Publication Date: Sep 11, 2018
• Publication Date: Sep 11, 2018
• Deposit Date: Sep 17, 2018
• Publicly Available Date: Sep 17, 2018
• Journal: Brain Sciences
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 9
• Article Number: 175
• DOI: https://doi.org/10.3390/brainsci8090175
• Keywords: acetylation; ageing; alcoholism; alcohol-related brain damage; α-tubulin; β-tubulin; HDAC6; MAP-2; MAP-tau; pre-frontal cortex
• Public URL: https://nottingham-repository.worktribe.com/output/1077001
• Publisher URL: http://www.mdpi.com/2076-3425/8/9/175
• Contract Date: Sep 17, 2018