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

Western diet (WD) consumption during development yields long-lasting memory impairments, yet the underlying neurobiological mechanisms remain elusive. Here we developed an early life WD rodent model to evaluate whether dysregulated hippocampus (HPC) acetylcholine (ACh) signaling, a pathology associated with memory impairment in human dementia, is causally-related to WD-induced cognitive impairment. Rats received a cafeteria-style WD (access to various high-fat/high-sugar foods; CAF) or healthy chow (CTL) during the juvenile and adolescent periods (postnatal days 26-56). Behavioral, metabolic, and microbiome assessments were performed both before and after a 30-day healthy diet intervention beginning at early adulthood. Results revealed CAF-induced HPC-dependent contextual episodic memory impairments that persisted despite healthy diet intervention, whereas CAF was not associated with long-term changes in body weight, body composition, glucose tolerance, anxiety-like behavior, or gut microbiome. HPC immunoblot analyses after the healthy diet intervention identified reduced levels of vesicular ACh transporter in CAF vs. CTL rats, indicative of chronically reduced HPC ACh tone. To determine whether these changes were functionally related to memory impairments, we evaluated temporal HPC ACh binding via ACh-sensing fluorescent reporter

Déclaration de conflit d'intérêts

Conflict of Interest The authors declare no competing interests.