Defining the Microglia Response during the Time Course of XXXX .

@entity32 @entity19 @entity1579 @entity27465 @entity179 @entity17224
@entity32 has been proposed as a major component of @entity179 , although the precise role it plays has yet to be defined. We examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a @entity179 . Initially, we performed an extensive reanalysis of a large study of @entity1579 , where the transcriptome of @entity19 brains had been monitored throughout the time course of disease. Our analysis has provided a detailed classification of the disease-associated genes based on cell type of origin and gene function. This revealed that the genes upregulated during disease, regardless of the strain of @entity19 or @entity27465 , are expressed predominantly by activated microglia. In order to study the microglia contribution more specifically, we established a @entity19 model of @entity1579 in which the 79A @entity19 prion strain was introduced by an intraperitoneal route into BALB/cJ(Fms-EGFP/-) @entity19 , which express enhanced green fluorescent protein under the control of the @entity17224 operon. Samples were taken at time points during disease progression, and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease-specific, highly proinflammatory signature in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the importance of microglia within the @entity1579 process and identifies the nature of the response through gene expression analysis of isolated microglia. IMPORTANCE: @entity32 has been proposed as a major component of @entity179 . We have examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a @entity19 @entity179 . Our study demonstrates that genes upregulated throughout the disease process are expressed predominantly by microglia. A disease-specific, highly proinflammatory signature was observed in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the important contribution of microglia to a chronic @entity179 process.
