From Ritika Samant
Growing evidence suggests an integral role of the immune system in the pathogenesis of Parkinson’s disease (PD). In the post-mortem PD brain, microglia, elevated cytokine expression, and their activation correlates with the localization and abundance of α-synuclein aggregates. While their presence indicates active neuroinflammation, activated microglia also operate along a pro-inflammatory/wound-healing gradient and can be functionally classified. A functional classification of activated microglia is disease-associated microglia (DAMs), widely identified by the TREM-2 receptor. DAMs, characterized in Alzheimer’s disease as disease mitigating, have not been explored in PD. DAM distribution is important to characterize because of its potential disease mitigating or exacerbating role. Specifically, DAM distribution, neuroinflammatory, and neurodegenerative significance have not been examined in the rat pre-formed fibril (PFF) model of PD. The ongoing goals of this project are to determine (1) whether DAMs are present in and (2) if DAM markers change over time in pathology. To accomplish these goals, we are employing a PFF model of α-synuclein propagation in the rat brain. Injection of PFFs seeds the aggregation of endogenous α-synuclein, resulting in progressive pathology in the rat brain. Using immunohistochemistry and confocal microscopy, we present our preliminary findings on whether DAMs are present in Sprague Dawley and correlate with PD pathology.