Tauopathy and alcohol consumption interact to alter locus coeruleus excitatory transmission and excitability in male and female mice.

Autor: Downs AM; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States., Catavero CM; Graduate Program in Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States., Kasten MR; Department of Otolaryngology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States., McElligott ZA; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States. Electronic address: zoemce@email.unc.edu.
Jazyk: angličtina
Zdroj: Alcohol (Fayetteville, N.Y.) [Alcohol] 2023 Mar; Vol. 107, pp. 97-107. Date of Electronic Publication: 2022 Sep 20.
DOI: 10.1016/j.alcohol.2022.08.008
Abstrakt: Alcohol use disorder is a major public health concern in the United States. Recent work has suggested a link between chronic alcohol consumption and the development of tauopathy disorders, such as Alzheimer's disease and frontotemporal dementia. However, relatively little work has investigated changes in neural circuitry involved in both tauopathy disorders and alcohol use disorder. The locus coeruleus (LC) is the major noradrenergic nucleus in the brain and is one of the earliest sites to be affected by tau lesions. The LC is also implicated in the rewarding effects of ethanol and alcohol withdrawal. In this study we assessed effects of long-term ethanol consumption and tauopathy on the physiology of LC neurons. Male and female P301S mice, a humanized transgenic mouse model of tauopathy, underwent 16 weeks of intermittent access to 20% ethanol from 3 to 7 months of age. We observed higher total alcohol consumption in female mice regardless of genotype. Male P301S mice consumed more ethanol and had a greater preference for ethanol than wild-type (WT) males. At the end of the drinking study, LC function was assessed using ex vivo whole cell electrophysiology. We found significant changes in excitatory inputs to the LC due to both ethanol and genotype. We found significantly increased excitability of the LC due to ethanol with greater effects in female P301S mice than in female WT mice. Our study identifies significant changes in the LC due to interactions between tauopathy and long-term ethanol use. These findings could have important implications regarding LC activity and changes in behavior due to both ethanol- and tauopathy-related dementia.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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