Regulators of Microglia Homeostasis and Characterization of CD39-/- Epileptic Mice
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CitationLanser, Amanda. 2017. Regulators of Microglia Homeostasis and Characterization of CD39-/- Epileptic Mice. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractThe immune system plays an important role in both normal development and the progression of neurological diseases. Microglia, the resident macrophages of the central nervous system (CNS), respond rapidly to changes in the local microenvironment in which they may prevent, suppress or initiate disruptions in CNS homeostasis depending on the context. We found increased proinflammatory gene and microRNA (miRNA) signatures in microglia isolated from the spinal cord of SOD1G93A mice that model Amyotrophic Lateral Sclerosis (ALS), indicating a potential pathogenic role in the disease. In addition, we developed a reliable system to study microglia ex vivo and identify drivers of microglia quiescence. Both TGF-β1 and IFN-γ induced important microglial genes such as Fcrls and Cd39 respectively. Interestingly, global deletion of Cd39, an ecto-nucleoside triphosphate diphosphohydrolase (e-NTPDase), caused a robust handling-induced and spontaneous seizure phenotype that increased in severity with age. This behavioral phenotype did not coincide with gross neuroimmune abnormalities. However, the cerebrospinal fluid (CSF) of CD39-/- mice contained increased levels of ATP and decreased adenosine compared to wild type mice. Conditional deletion of CD39 on microglia did not induce seizures in adult mice suggesting that microglia were not involved in the seizure phenotype of these mice. Altogether these data contribute to our understanding of microglia ex vivo and in vivo and identify CD39 as being potentially important in the physiology of epilepsy.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41142051
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