Chronic Stress Exacerbates Hyperglycemia-Induced Depressive-Like Behavior in Male Mice

Among chronically ill populations, affective disorders remain underdiagnosed and undertreated. A high degree of comorbidity exists between diabetes and affective disorders, particularly depression and anxiety. While the mechanisms contributing to stress-induced affective dysregulation are currently being parsed out, a direct comparison between stress-induced and hyperglycemia-induced affective dysregulation would provide insight into more effective treatments for diabetic patients suffering from depression/anxiety. The present study was performed in order to explore the effects of chronic stress and hyperglycemia in a preclinical model. We observed distinct neuroinflammatory and behavioral profiles in response to chronic stress and chronic hyperglycemia. STZ-induced hyperglycemia was associated with increased depressive-like behavior, elevations in hippocampal Bdnf and Tnf-α expression, and elevations in prefrontal cortex Il-1β expression. Chronic stress produced alterations in anxiety-like behavior and decreased prefrontal cortex Il-1β expression. While chronic stress and hyperglycemia can individually produce affective dysregulation, their combination exacerbates the symptom burden and is indicative of distinct neurobiological mechanisms.