EXPLORING THE EFFECTS OF INTERMITTENT FASTING ON THE GUT-BRAIN AXIS AND STRESS-INDUCED DEPRESSION-LIKE PHENOTYPES IN MICE

Chronic stress is a major risk factor for the onset of major depressive disorder with alterations in gut-brain signaling and dysfunction of the hypothalamic-pituitary-adrenal-axis thought to play a role. Intermittent Fasting (IF) has emerged as a potential non-pharmacological approach to enhance brain function, including cognitive performance and mood regulation. We aim to investigate the effects of IF on gut-brain communication and stress-induced behavioral disturbances.
Using a model of depression induced by chronic unpredictable mild stress combined with IF in mice, behavioral phenotypes such as anxiety, social behavior, anhedonia and cognitive performance were assessed through the utilization of various behavioral assays including the open-field test (OFT) splash test (ST) and the social versus food paradigm test (SvFT) .
IF alleviated anxiety-like behavior, as evidenced by an increased time spent in the center zone of the OFT, independent of stress. In contrast, IF exacerbated stress-induced anhedonia, seen as reduced grooming behavior in the ST, but increased physical activity during the test. Furthermore, food exploration was diminished by IF independent of stress in the SvFT, while social interaction was not altered.
IF is widely regarded as a beneficial dietary strategy with numerous reported positive effects on metabolic and brain health. The present study confirms anxiolytic and activity-promoting effects of IF, while no consistent effects on stress-induced depression-like behavior were observed. Further research is warranted to investigate the context-dependent effects of IF on stress-induced depression and the underlying molecular and hormonal pathways involved.