Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling

• DOI: 10.1016/j.bbi.2024.03.015
• Publication Date: 2024-03-08T09:22:08Z
• Authors: Anna M.R. Hayes; Logan Tierno Lauer; Alicia E. Kao; Shan Sun; Molly E. Klug; Linda Tsan; Jessica J. Rea; Keshav S. Subrama...; Cindy Gu; Natalie Tanios; Arun Ahuja; Kristen N. Donohue; Léa Décarie-Spain; Anthony A. Fodor; Scott E. Kanoski
• Keywords: CTL*

Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an WD rodent model long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style (ad libitum access various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) juvenile and adolescent stages (postnatal days 26–56). Behavioral metabolic assessments were performed both before after intervention period beginning at adulthood. Results revealed HPC-dependent contextual episodic impairments in CAF rats that persisted despite intervention. Given dysregulated acetylcholine (ACh) signaling humans animal models, we examined protein markers of ACh tone dorsal (HPCd) CTL rats. significantly lower levels vesicular transporter HPCd vs. rats, indicating chronically reduced tone. Using intensity-based sensing fluorescent reporter (iAChSnFr) vivo fiber photometry targeting HPCd, next release object-contextual novelty recognition was highly predictive performance disrupted Neuropharmacological results showed alpha 7 nicotinic receptor agonist infusion training rescued deficits Overall, findings reveal functional connection linking intake dysregulation signaling, thereby identifying underlying mechanism WD-associated impairments.