2026-03-16 マサチューセッツ大学アマースト校
The locus coeruleus (outlined) of mice exposed to alcohol and stress show markedly more signs of oxidative stress (bottom) than the brains of mice that avoided the stress/alcohol cocktail (top).
＜関連情報＞
- https://www.umass.edu/news/article/umass-amherst-research-links-early-adult-drinking-middle-age-cognitive-decline
- https://onlinelibrary.wiley.com/doi/10.1111/acer.70273
慢性的なアルコール摂取とストレスがマウスの中年期の認知機能と青斑核の完全性に及ぼす影響 Impact of chronic alcohol and stress on midlife cognition and locus coeruleus integrity in mice
O. Revka, S. J. Belculfine, L. Fitts, K. E. Nippert, C. A. F. Teves, P. M. Reis, S. Tenney, B. E. Packer, I. Garcia Alvarez, O. Milstein, M. Coutinho da Silva, D. E. Moorman, E. M. Vazey
Alcohol, Clinical and Experimental Research Published: 09 March 2026
DOI:https://doi.org/10.1111/acer.70273
Abstract
Background
Excessive alcohol consumption and stress are associated with structural and functional alterations in the brain and impaired cognition. However, the persistence of long-term neural impacts after alcohol and stress is less understood. This study investigated midlife cognition and neuropathological changes following a history of alcohol and stress exposure.
Methods
C57BL/6J mice acclimated to ethanol drinking (15% v/v) before exposure to four cycles of alternating chronic intermittent ethanol (CIE) vapor exposure and repeated forced swim stress (FSS), with control groups exposed to air and no stress (AIR/NS). After 3 months of abstinence, mice were evaluated at midlife (11 months old) on volitional drinking and a final CIE/FSS challenge for stress-induced drinking. Spatial learning and cognitive flexibility were assessed using the Barnes maze before brains were collected to evaluate locus coeruleus (LC) integrity at 12 months old.
Results
CIE/FSS increased volitional alcohol intake, and this drinking phenotype persisted through to midlife despite extended abstinence. CIE/FSS mice showed intact spatial learning but impaired flexibility in the Barnes maze reversal phase. Flexibility impairments were driven by decreased time in the target quadrant and increased errors during the reversal test compared with AIR/NS. Furthermore, CIE/FSS mice showed pathological measures of reduced LC integrity common to dementia-related disorders, including elevated markers of oxidative stress, apoptosis, and reduced autoinhibitory function.
Conclusions
Our findings highlight the long-lasting impact of alcohol and stress exposure on cognition, with flexibility impairments persisting into midlife. In addition to cognitive changes, alcohol and stress history produced pathological changes in the LC, an area known to mediate cognitive flexibility via its forebrain projections. Together, these results give insight into the long-lasting impacts of chronic alcohol and stress and how they may accelerate age-related cognitive decline.
