Minocycline alleviates Gulf War Illness rats via altering gut microbiome, attenuating neuroinflammation and enhancing hippocampal neurogenesis.

ABSTRACT

Accumulating evidences suggest that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intends to investigate whether the treatment of minocycline maintains better cognition and mood function in a rat model of GWI and the potential mechanism. Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected. We found that minocycline treatment induces better cognitive and mood function in the GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possibly related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline as a potential prophylactic or therapeutic agent for the treatment of GWI.