UNASSIGNED: Astrocytes and microglia are commonly involved in a wide variety of CNS pathologies. However, they are typically involved in a secondary response in which many cell types are affected simultaneously and therefore it is difficult to know their contributions to the pathology. Here, we show that pathological astrocytes in a @entity19 model of @entity26008 (AxD; @entity9327 (Tg); @entity9327 (+/ @entity65454 )) cause a pronounced immune response. We have studied the inflammatory response in the hippocampus and spinal cord of these @entity19 and have found marked microglial activation, which follows that of astrocytes in a spatial pathological progression, as shown by increased levels of @entity9271 and microglial cell ( @entity9271 +) density. RNA sequencing and subsequent @entity74 ( @entity74 ) analysis revealed that a majority of the most upregulated genes in @entity9327 (Tg); @entity9327 (+/ @entity65454 ) @entity19 are directly associated with immune function and that cytokine and chemokine @entity74 attributes represent nearly a third of the total immune attributes. Cytokine and chemokine analysis showed @entity15369 and @entity1750 to be the most and earliest increased molecules, showing concentrations as high as EAE or @entity64 models. @entity15369 was localized exclusively to astrocytes while @entity1750 was also present in microglia. Despite the high levels of @entity15369 and @entity1750 , T cell infiltration was mild and no B cells were found. Thus, mutations in @entity9327 are sufficient to trigger a profound inflammatory response. The cellular stress caused by the accumulation of @entity9327 likely leads to the production of inflammatory molecules and microglial activation. Examination of @entity1 AxD CNS tissues also revealed microglial activation and T cell infiltrates. Therefore, the inflammatory environment may play an important role in producing the @entity528 and @entity410 of AxD.

Astrocyte pathology in XXXX causes a marked inflammatory environment.

@entity1 :: ('9606', 'Species') :: ['human'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizures'] @entity64 :: ('MESH:D020521', 'Disease') :: ['stroke'] @entity65454 :: ('p|SUB|R|236|H', 'ProteinMutation') :: ['R236H'] @entity9327 :: ('14580(Tax:10090)', 'Gene') :: ['GFAP', 'Gfap'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1750 :: ('20296(Tax:10090)', 'Gene') :: ['CCL2'] @entity9271 :: ('114737(Tax:10090)', 'Gene') :: ['Iba1'] @entity74 :: ('MESH:D030342', 'Disease') :: ['gene ontology', 'GO'] @entity26008 :: ('MESH:D038261', 'Disease') :: ['Alexander disease'] @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal dysfunction'] @entity15369 :: ('15945(Tax:10090)', 'Gene') :: ['CXCL10']
@entity26008 :: (MESH:D038261,Disease) :: ['Alexander disease']
