The Impact of a Mediterranean-Based Diet on Cognitive, Inflammatory, and Neurotrophic Impairments Induced by a Chronic Social Defeat Stressor in Male C57BL/6N Mice

Abstract

Background: Stress-related neuropsychiatric disorders have overlapping impairments in social and non-social cognition. Limited efficacy of treatments targeting these symptoms and the continued increase in prevalence in these disorders has necessitated alternative strategies. The Mediterranean (Med) diet has been shown to improve depression, anxiety, and cognitive deficits in clinical studies. Using a mouse model of chronic social stress, this study investigated the potential of a mouse-adjusted Med-based dietary intervention to mitigate social and non-social cognitive impairments and limit changes in brain neurotrophic and inflammatory factors.

Methods: Male C57BL/6N mice were randomly assigned to a Control or a Med-based diet. After a 14-day acclimatization period to the diets, both groups were either subjected to 10 consecutive days of chronic social defeat stress (CSDS) or to a no stressor control condition. Cognitive tests were conducted 24 hours after the last stressor or control session. The ventral hippocampus was collected 24 hours following the last cognitive test and analyzed for the mRNA expression of pro-inflammatory cytokines, microglial markers, and neurotrophic factors.

Results: The CSDS regimen increased social avoidance behaviours and altered the hippocampal expression of neurotrophin-3 and Tropomyosin receptor kinase B. In CSDS mice, the Med-based diet improved long-term memory and reduced hippocampal tumor necrosis factor alpha but promoted social avoidance behaviours, impaired spatial reference memory, and decreased hippocampal brain-derived neurotrophic factor.

Conclusion: Dietary interventions in male mice may have differential effects on cognitive and hippocampal health in the context of chronic social stress, requiring further investigation into its use as an adjunctive therapy for cognitive deficits in stress-related neuropsychiatric disorders.