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Deficiency Of Tnf Receptors Suppresses Microglial Activation And Alters The Susceptibility Of Brain Regions To Mptp-Induced Neurotoxicity: Role Of Tnf-Α, Krishnan Sriram, Joanna M. Matheson, Stanley A. Benkovic, Diane B. Miller, Michael I. Luster, James P. O'Callaghan

Public Health Resources

Enhanced expression of tumor necrosis

factor (TNF) -α, is associated with the neuropathological

effects underlying disease-, trauma- and chemically

induced neurodegeneration. Previously, we have shown

that deficiency of TNF receptors protects against

MPTP-induced striatal dopaminergic neurotoxicity,

findings suggestive of a role for TNF-α in neurodegeneration.

Here, we demonstrate that deficiency of TNF

receptors suppresses microglial activation and alters

the susceptibility of brain regions to MPTP. MPTPinduced

expression of microglia-derived factors,

TNF-α, MCP-1, and IL-1α, preceded the degeneration

of striatal dopaminergic nerve terminals and astrogliosis,

as assessed by loss of striatal dopamine and TH, …