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Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB
Hao Chen1, Kaitlyn Hinz1, Chen Zhang1
1Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Biomolecules
|January 8, 2025
Summary
Aging significantly impairs brain autophagy and spatial memory more than alcohol consumption. Chronic alcohol intake did not worsen age-related cognitive decline or autophagy reduction in mice.
Area of Science:
- Neuroscience
- Cellular Biology
- Aging Research
Background:
- Alcohol consumption's impact on Alzheimer's disease (AD) risk is unclear, with autophagy potentially mediating this link.
- Autophagy, crucial for cellular homeostasis, is regulated by Transcription factor EB (TFEB), influencing lysosomal and autophagy-related gene expression.
Purpose of the Study:
- To investigate if chronic alcohol consumption exacerbates age-related decline in TFEB-mediated lysosomal biogenesis and cognitive function.
- To determine alcohol's effect on brain TFEB activity and autophagy in young versus aged mice.
Main Methods:
- Exposure of young and aged mice to alcohol-feeding paradigms.
- Assessment of biochemical, transcriptome, histological, and behavioral endpoints, including TFEB activity and autophagy markers (SQSTM1/p62, LC3-II).
- Evaluation of spatial memory using Morris Water and Barnes Maze tasks.
Main Results:
- In young mice, alcohol reduced hippocampal TFEB and increased autophagy markers and phosphorylated Tau.
- Aged mice exhibited lower hippocampal TFEB activity than young mice; alcohol did not worsen this age-related decline.
- Aging impaired spatial memory acquisition more than alcohol consumption, with alcohol showing minimal negative or even slight positive effects in aged mice.
Conclusions:
- Aging causes more significant reductions in brain autophagy flux and spatial memory deficits than alcohol consumption.
- Chronic alcohol exposure does not exacerbate age-related declines in TFEB-mediated autophagy or spatial memory.
