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Vitamin E suppression of microglial activation is neuroprotective
Author(s) -
Li Yuekui,
Liu Ling,
Barger Steven W.,
Mrak Robert E.,
Griffin W. Sue T.
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1208
Subject(s) - neuroprotection , microglia , p38 mitogen activated protein kinases , tumor necrosis factor alpha , mapk/erk pathway , nitric oxide , biology , kinase , inflammation , microbiology and biotechnology , pharmacology , chemistry , endocrinology , immunology
Abstract Neurotoxic microglial–neuronal interactions have been implicated in the pathogenesis of various neurodegenerative diseases such as Alzheimer's disease, and vitamin E has been shown to have direct neuroprotective effects. To determine whether vitamin E also has indirect neuroprotective effects through suppression of microglial activation, we used a microglial–neuronal coculture. Lipopolysaccharide (LPS) treatment of a microglial cell line (N9) induced a time‐dependent activation of both p38 mitogen‐activated protein kinase (p38 MAPK) and nuclear factor‐κB (NFκB), with consequent increases in interleukin‐1α (IL‐1α), tumor necrosis factor‐α (TNF‐α), and nitric oxide (NO) production. Differentiated neuronal cells (PC12 cells treated with nerve growth factor) exhibited marked loss of processes and decreased survival when cocultured with LPS‐activated microglia. Preincubation of microglia with vitamin E diminished this neurotoxic effect, independently of direct effects of the antioxidant on the neuronal cells. Microglial NO production and the induction of IL‐1α and TNFα expression also were attenuated by vitamin E. Such antiinflammatory effects of vitamin E were correlated with suppression of p38 MAPK and NFκB activation and were mimicked by an inhibition of either p38 MAPK (by SB203580) or NFκB (by decoy oligonucleotides). These results suggest that, in addition to the beneficial effects of providing direct antioxidant protection to neurons reported by others, vitamin E may provide neuroprotection in vivo through suppression of signaling events necessary for microglial activation. J. Neurosci. Res. 66:163–170, 2001. Published 2001 Wiley‐Liss, Inc.