Investigating a novel microglial phenotype in a genetic model of Parkinson's Disease

Microglia are the brain resident immune cells. They play a key role in protecting the central nervous system as well as in maintaining its homeostasis. Recently, the role of microglia has been studied in pathological conditions, including neurodegenerative diseases and aging, leading to the discovery of a new microglial subpopulation, named Disease Associated Microglia (DAM) or microglial neurodegenerative phenotype (MGnD). RNA sequencing analysis reveals that DAM/MGnD express a panel of peculiar markers including the Clec7A gene which encodes for Dectin-1 protein. Here, we focused our studies on the characterization of Dectin1-associated phenotypes in Parkinson’s Disease (PD) by using a genetic murine model of the pathology. By applying immunofluorescence techniques, we revealed that Dectin1 positive microglia is enhanced, and it tends to cluster in the dorsal striatum of the PD mice compared to the wildtype controls. Additional analysis in primary microglial cells from these mice further confirms Dectin-1 overexpression in our PD model. Moreover, preliminary data suggest that pathogenic microglia display increased susceptibility to oxidative stress as well as altered phagocytic activity. Of note, unpublished data from our collaborators proposed Dectin-1 as a marker for dark microglia, a cellular population that is highly represented in disease states. Current studies are dedicated to characterizing PD mice in terms of dark microglia and correlating dark microglia visualization to Dectin-1 expression. Overall, this study suggests the presence of a novel microglial subtype, the Dectin1+ cells, in our model of PD pathology.