Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory

摘要: Stringent glucose demands render the brain susceptible to disturbances in supply of this main source energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments arise from disturbed regulation remains unclear. Here we show that social defeat (CSD) adult male mice induces hyperglycemia directly affects spatial memory performance. Stressed developed impaired metabolism peripherally as well (demonstrated by PET induced metabolic bioluminescence imaging), which was accompanied hippocampus-related impairments. Importantly, phenotype pertained subset stressed could be linked early 2 days post-CSD. Based on criterion, ∼40% had high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance biomarker emerges effects glucose-lowering sodium cotransporter inhibitor empagliflozin, because upon dietary treatment, identified having high demonstrated restored normalized metabolism. Conversely, reducing levels empagliflozin did not display stress-induced (resilient mice) their default-intact We conclude developing after threatens long-term homeostasis causes dysfunction. Our findings explain comorbidity between stress-related disorders, depression diabetes, suggest both types disorders originate excessive cerebral accumulation.