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• W1570444420 startingPage "145" @default.
• W1570444420 abstract "In vitro and in vivo models of Parkinson's disease were used to investigate whether TNF-α plays a major role in the enhancement of the microglial response and dopaminergic degeneration induced by brain angiotensin hyperactivity. Treatment of primary mesencephalic cultures with low doses of the neurotoxin MPP+ induced a significant loss of dopaminergic neurons, which was enhanced by cotreatment with angiotensin II and inhibited by TNF-α inhibitors. Treatment of primary cultures with angiotensin induced a marked increase in levels of TNF-α, which was inhibited by treatment with angiotensin type-1-receptor antagonists, NADPH-oxidase inhibitors and NFK-β inhibitors. However, TNF-α levels were not significantly affected by treatment with angiotensin in the absence of microglia. The microglial origin of the angiotensin-induced increase in TNF-α levels was confirmed using dopaminergic (MES 23.5) and microglial (N9) cell lines. Inhibition of the microglial Rho-kinase activity also blocked the AII-induced increase in TNF-α levels. Treatment of the dopaminergic cell line with TNF-α revealed that NFK-β activation mediates the deleterious effect of microglial TNF-α on dopaminergic neurons. Treatment of mice with MPTP also induced significant increases in striatal and nigral TNF-α levels, which were inhibited by angiotensin type-1-receptor antagonists or NFK-β inhibitors. The present results show that microglial TNF-α plays a major role in angiotensin-induced dopaminergic cell death and that the microglial release of TNF-α is mediated by activation of angiotensin type-1 receptors, NADPH-oxidase, Rho-kinase and NFK-β. GLIA 2014;62:145–157" @default.
• W1570444420 created "2016-06-24" @default.
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• W1570444420 date "2013-11-23" @default.
• W1570444420 modified "2023-10-18" @default.
• W1570444420 title "Microglial TNF-α mediates enhancement of dopaminergic degeneration by brain angiotensin" @default.
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• W1570444420 doi "https://doi.org/10.1002/glia.22595" @default.
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