Role of the Sirt6/Hmgb1 pathway in neuroinflammation of Sleep deprivation-induced depressed mice

Many depressed patients exhibit sleep disorders, which in turn are a driver of the onset of depression. There is substantial evidence that neuroinflammation plays a key role in the pathophysiology and treatment of depression. Here, we investigated the mechanisms by which sleep deprivation (SD) induced anxiety-depressive-like behaviors in mice and the role of neuroinflammation in it. Adult male C57BL/6J mice were selected for the construction of a depression model by SD instrumentation. Five behavioral tests were used to evaluate the anxiety and depressive-like behaviors of the mice. H＆E staining and Nissl staining were utilized to detect cellular morphology and neuronal changes. Real-time quantitative fluorescence PCR (RT-qPCR) was carried out to regulate the mRNA levels of the clock gene, Silent information regulators 6 (Sirt6), High mobility group box-1 (Hmgb1), and pro-inflammatory factors. Western blot and immunofluorescence proved that SD increased the levels of clock genes and Sirt6/Hmgb1 pathway proteins. Our research showed that SD can be used as a reliable mouse model of depression. The pathological mechanism may be that SD regulated the Sirt6/Hmgb1 pathway and affected the transcription of clock genes, leading to inflammatory infiltration in the mPFC region of mice.