@entity22230 , the sole known signaling receptor for the TNF family member @entity22229 , is inducibly expressed in the central nervous system (CNS) in endothelial cells, astrocytes, microglia, and neurons. There is increasing recognition of the importance of the @entity22229 / @entity22230 pathway in @entity10469 , including experimental autoimmune @entity1651 and @entity12319 . Previously, we had found that @entity22230 knockout lupus-prone MRL/lpr @entity19 display significantly attenuated neuropsychiatric manifestations. To investigate whether this improvement in disease is secondary to inhibition of @entity22229 / @entity22230 signaling within the CNS or the periphery, and determine whether @entity22229 -mediated neuropsychiatric effects are strain dependent, we performed intracerebroventricular (ICV) injection of Fc- @entity22229 or an isotype matched control protein to C57Bl6/J non-autoimmune @entity19 . We found that Fc- @entity22229 injected C57Bl6/J @entity19 developed significant @entity308 -like behavior and @entity73 . Inflammatory mediators associated with @entity75 , including @entity1750 , C3, and iNOS, were significantly elevated in the brains of Fc- @entity22229 treated @entity19 . Furthermore, Fc- @entity22229 directly increased blood brain barrier (BBB) permeability, as demonstrated by increased IgG deposition in the brain and reduced @entity22440 expression. Finally, Fc- @entity22229 increased apoptotic cell death in the cortex and hippocampus. In conclusion, @entity22229 can contribute to lupus-associated @entity4934 including @entity308 and @entity73 by acting within the CNS to enhance production of inflammatory mediators, promote disruption of the BBB, and induce apoptosis in resident brain cells. Our study provides further support that the @entity22229 / @entity22230 signaling pathway may be a potential therapeutic target for inflammatory diseases involving the CNS.

Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces @entity308 -like behavior and XXXX in non-autoimmune @entity19 .

@entity308 :: ('MESH:D003866', 'Disease') :: ['depression'] @entity1750 :: ('20296(Tax:10090)', 'Gene') :: ['CCL2'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive dysfunction'] @entity75 :: ('MESH:D001927', 'Disease') :: ['lupus brain disease'] @entity22440 :: ('11829(Tax:10090)', 'Gene') :: ['aquaporin-4'] @entity4934 :: ('MESH:D019954', 'Disease') :: ['neurobehavioral deficits'] @entity22229 :: ('21944(Tax:10090)', 'Gene') :: ['TWEAK'] @entity22230 :: ('27279(Tax:10090)', 'Gene') :: ['Fn14'] @entity10469 :: ('MESH:D020274', 'Disease') :: ['autoimmune neurologic conditions'] @entity1651 :: ('MESH:D004679', 'Disease') :: ['encephalomyelitis'] @entity12319 :: ('MESH:D020945', 'Disease') :: ['neuropsychiatric lupus']
@entity73 :: (MESH:D003072,Disease) :: ['cognitive dysfunction']
