Enhanced microglial pro-inflammatory response to lipopolysaccharide correlates with brain infiltration and blood-brain barrier dysregulation in a @entity19 model of XXXX .

@entity32 @entity19 @entity3207 @entity21324 @entity1200
UNASSIGNED: Microglia are a proliferative population of resident brain macrophages that under physiological conditions self-renew independent of hematopoiesis. Microglia are innate immune cells actively surveying the brain and are the earliest responders to injury. During aging, microglia elicit an enhanced @entity1200 also referred to as 'priming'. To date, it remains unknown whether @entity3207 affects the proliferative capacity and induces priming of microglia. We addressed this issue using early (first-generation G1 @entity21324 (-/-) )- and late-generation (third-generation G3 and G4 @entity21324 (-/-) ) telomerase-deficient @entity19 , which carry a homozygous deletion for the telomerase RNA component gene ( @entity21324 ). Late-generation @entity21324 (-/-) microglia show @entity3207 and decreased proliferation efficiency. Under physiological conditions, gene expression and functionality of G3 @entity21324 (-/-) microglia are comparable with microglia derived from G1 @entity21324 (-/-) @entity19 despite changes in morphology. However, after intraperitoneal injection of bacterial lipopolysaccharide (LPS), G3 @entity21324 (-/-) microglia @entity19 show an enhanced pro-inflammatory response. Nevertheless, this enhanced inflammatory response was not accompanied by an increased expression of genes known to be associated with age-associated microglia priming. The increased inflammatory response in microglia correlates closely with @entity32 , a loss of blood-brain barrier integrity, and infiltration of immune cells in the brain parenchyma in this @entity19 model of @entity3207 .
