Ethanol exposure alters Alzheimer's-related pathology, behavior, and metabolism in APP/PS1 mice

• DOI: 10.1016/j.nbd.2022.105967
• Publication Date: 2022-12-16T16:23:40Z
• Authors: Stephen M. Day; Stephen C. Gironda; Caitlin W. Clarke; J. Andy Snipes; Noelle I. Nicol; Hana Kamran; Warner Vaughan; Jeffrey L. Weiner; Shannon L. Macauley
• Keywords: Microdialysis

Epidemiological studies identified alcohol use disorder (AUD) as a risk factor for Alzheimer's disease (AD), yet there is conflicting evidence on how promotes AD pathology. In this study, 10-week moderate two-bottle choice drinking paradigm was used to identify chronic ethanol exposure alters amyloid-β (Aβ)-related pathology, metabolism, and behavior. Ethanol-exposed APPswe/PSEN1dE9 (APP/PS1) mice showed increased brain atrophy an number of amyloid plaques. Further analysis revealed that led shift in the distribution plaque size cortex hippocampus. developed greater smaller plaques, potentially setting stage proliferation later life. Ethanol APP/PS1 also exhibited deficits nest building, metric self-care, well locomotor activity central zone exploration open field test. diurnal feeding behavior which associated with changes glucose homeostasis intolerance. Complementary vivo microdialysis experiments were measure acute directly modulates Aβ hippocampal interstitial fluid (ISF). Acute transiently ISF levels, suggesting affects cerebral metabolism. selectively Aβ40, but not Aβ42, levels during withdrawal. Lastly, N-methyl-d-aspartate receptor (NMDAR) decreased γ-aminobutyric acid type-A (GABAAR) mRNA indicating potential hyperexcitable brain's excitatory/inhibitory (E/I) balance. Collectively, these suggest may increase deposition by disrupting metabolism E/I Furthermore, study provides culminates interaction between AD-related phenotypes potentiation behavioral dysfunction, metabolic impairment.