Early Activation of STAT3 Regulates Reactive Astrogliosis Induced by Diverse Forms of Neurotoxicity

摘要: Astrogliosis, a cellular response characterized by astrocytic hypertrophy and accumulation of GFAP, is hallmark all types central nervous system (CNS) injuries. Potential signaling mechanisms driving the conversion astrocytes into "reactive" phenotypes differ with respect to injury models employed can be complicated factors such as disruption blood-brain barrier (BBB). As denervation tools, neurotoxicants have advantage selective targeting brain regions cell types, often sparing BBB. Previously, we found that neuroinflammation activation JAK2-STAT3 pathway in precedes up regulation GFAP MPTP mouse model dopaminergic neurotoxicity. Here show multiple mechanistically distinct neurotoxicity (MPTP, AMP, METH, MDA, MDMA, KA, TMT) engender same neuroinflammatory STAT3 responses specific targeted each neurotoxicant. The effects seen for TMT could generalized rat, demonstrating cross-species validity activation. Pharmacological antagonists neurotoxic blocked responses, pSTAT3tyr705 induction, indicating damage neuronal targets instigated astrogliosis. Selective deletion from conditional knockout mice markedly attenuated MPTP-induced Monitoring translocation GFAP-positive cells indicated MPTP, METH KA on were localized astrocytes. These findings strongly implicate broadly triggered We also observed, however, acute known inflammogen, LPS, activate CNS tissue without inducing classical signs Thus, phase neurotoxicity-induced astrogliosis both signal through but appear do so different modules, perhaps types.