Western diet consumption impairs memory function via dysregulated hippocampus acetylcholine signaling.

Autor: Hayes AMR; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Lauer LT; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Kao AE; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Sun S; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA., Klug ME; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Tsan L; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA., Rea JJ; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA., Subramanian KS; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA., Gu C; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Tanios N; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Ahuja A; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Donohue KN; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Décarie-Spain L; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA., Fodor AA; Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA., Kanoski SE; Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA. Electronic address: kanoski@usc.edu.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2024 May; Vol. 118, pp. 408-422. Date of Electronic Publication: 2024 Mar 08.
DOI: 10.1016/j.bbi.2024.03.015
Abstrakt: Western diet (WD) consumption during early life developmental periods is associated with impaired memory function, particularly for hippocampus (HPC)-dependent processes. We developed an early life WD rodent model associated with long-lasting HPC dysfunction to investigate the neurobiological mechanisms mediating these effects. Rats received either a cafeteria-style WD (ad libitum access to various high-fat/high-sugar foods; CAF) or standard healthy chow (CTL) during the juvenile and adolescent stages (postnatal days 26-56). Behavioral and metabolic assessments were performed both before and after a healthy diet intervention period beginning at early adulthood. Results revealed HPC-dependent contextual episodic memory impairments in CAF rats that persisted despite the healthy diet intervention. Given that dysregulated HPC acetylcholine (ACh) signaling is associated with memory impairments in humans and animal models, we examined protein markers of ACh tone in the dorsal HPC (HPCd) in CAF and CTL rats. Results revealed significantly lower protein levels of vesicular ACh transporter in the HPCd of CAF vs. CTL rats, indicating chronically reduced ACh tone. Using intensity-based ACh sensing fluorescent reporter (iAChSnFr) in vivo fiber photometry targeting the HPCd, we next revealed that ACh release during object-contextual novelty recognition was highly predictive of memory performance and was disrupted in CAF vs. CTL rats. Neuropharmacological results showed that alpha 7 nicotinic ACh receptor agonist infusion in the HPCd during training rescued memory deficits in CAF rats. Overall, these findings reveal a functional connection linking early life WD intake with long-lasting dysregulation of HPC ACh signaling, thereby identifying an underlying mechanism for WD-associated memory impairments.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: