Brain-Metabolic axis: Molecular mechanism of exacerbated depression-like behaviors in a diabetes mellitus model

Epidemiological evidence has suggested that the comorbidity of diabetes mellitus (DM) and depression mutually exacerbate their pathophysiology. However, the underlying molecular mechanism of the interaction of each disorder remains unclear. To address this question, we established a new comorbid mice model of two conditions. A series of behavioral analyses revealed that the comorbid mice exhibited a severer anhedonia-like behavior than depression model mice. Furthermore, RNA sequence analyses showed that pathways involved in pH homeostasis and inflammation were altered in the comorbid mice. Therefore, these results suggested that ameliorating abnormal pH and inflammation of the diabetic brain could be novel treatment strategies for depressive-related conditions.