Oleocanthal Ameliorates Metabolic and Behavioral Phenotypes in a Mouse Model of Alzheimer’s Disease

Abstract

Aging is a major risk factor for Alzheimer’s disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood–brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

Extra-Virgin Olive Oil in Alzheimer’s Disease: A Comprehensive Review of Cellular, Animal, and Clinical Studies

“…Notably, OC effectively restored metabolic parameters and alleviated anxiety-like behavior and sleep disturbances. These outcomes suggest that OC counteracts the metabolic and behavioral disruptions associated with AD [84]. The beneficial effects of OC and ligstroside have also been confirmed in an aging mouse model, namely, NMRI mice [70].…”

“…In another comprehensive study on the protective effect of OC, wild-type and 5xFAD mouse models were utilized to investigate the complex relationship between aging (4 and 9 months old), AD, and metabolic-behavioral changes without and with OC administered at 10 mg/kg for 3 months [84]. The Promethion cage system ® was used to monitor changes in physiological, metabolic, and behavioral parameters with age and AD pathology.…”