Investigating the role of CNS-derived neuroinflammation in stress and optogenetic model of depression in female and male mice

There is ample evidence for the role of inflammatory signaling pathways in depression. However, in these studies, depression was modeled either by bacterial endotoxins or by acute stress, usually studied only in male animals and only in one brain region. In this thesis, HMGB1, S100, NF-KB and microglia were marked with immunohistochemical methods to investigate inflammatory processes in brain regions implicated in the pathophysiology of depression, namely hippocampus, anterior cingulate cortex and nucleus accumbens in three different models of depression: acute stress, chronic stress and optogenetic stimulation of the anterior cingulate cortex. As a result, both behavioral hopelessness and decreased grooming were observed in response to acute stress in males, while behavioral hopelessness alone increased in females. Similarly, while the short-term memory performance of the male chronic stress group deteriorated; it did not alter the short-term memory performance of female mice. Hippocampus-dependent short-term memory performance was impaired by chronic stress only in males and by optogenetic ACC stimulation only in females. Chronic stress only increased depression-like behaviors and not alter anxiety-like behaviors, while optogenetic ACC stimulation increased both depression-like and anxiety-like behaviors. Acute stress led to a higher increase in inflammatory molecules than chronic stress. In the optogenetic model of depression, changes in inflammatory molecules were most evident in the hippocampus. These findings suggest that different models of depression trigger different inflammatory processes in the ACC, NA, and hippocampus, which may explain the differences in depression and anxiety-like behaviors observed between genders. Key words: depression, neuroinflammation, acute and chronic stress, optogenetic ACC stimulation, gender relationship This study is supported by TUBİTAK SBAG (118S558).