Behavioral and molecular consequences of a ‘double-hit’ challenge on the pathogenesis of mouse models of depression and amyotrophic lateral sclerosis (ALS)

This dissertation explores the effects of neuroinflammation on emotional abnormalities in two mouse models of neuropsychiatric disorders: chronic stress-induced depression and a transgenic mouse model of Amyotrophic lateral sclerosis. It investigates the 'double-hit' effects of chronic stress and systemic inflammation, revealing exacerbated depressive-like behavior. The role of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) in predisposition to depression is examined, highlighting the link between neuroinflammation and depressive syndrome. The study concludes by comparing the therapeutic potential of celecoxib (COX-2 inhibitor) and citalopram (antidepressant), suggesting that anti-inflammatory measures, including coxibs, could be valuable in preventing and treating depressive and neurodegenerative conditions. The research underscores the importance of understanding the interplay between etiological and environmental factors in neuropsychiatric disorders for improved translational research.