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TNF‐α receptor 1 deficiency enhances kainic acid–induced hippocampal injury in mice
Author(s) -
Lu MingOu,
Zhang XingMei,
Mix Eilhard,
Quezada Hernan Concha,
Jin Tao,
Zhu Jie,
Adem Abdu
Publication year - 2008
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.21600
Subject(s) - kainic acid , astrogliosis , neurodegeneration , microglia , hippocampal formation , tumor necrosis factor alpha , ccr2 , hippocampus , cx3cr1 , knockout mouse , receptor , gliosis , medicine , endocrinology , chemokine , neuroscience , immunology , chemokine receptor , chemistry , inflammation , biology , glutamate receptor , central nervous system , disease
The exact role of TNF‐α in excitotoxic neurodegeneration of the brain is unclear. To address this issue, the kainic acid (KA)–induced hippocampal injury model, a well‐characterized model of human neurodegenerative diseases, was used in TNF‐α receptor 1 (TNFR1)–knockout (TNFR1 −/− ) mice in the present study. After nasal application of a single dose of 40 mg of KA per kilogram body weight, TNFR1 −/− mice showed significantly more severe seizures than the wild‐type mice. In addition, obvious neurodegeneration, enhanced microglia activation, and astrogliosis in the hippocampus, as well as increased locomotor activity, were found in TNFR1 −/− mice compared with the wild‐type controls 8 days after KA delivery. Moreover, CC chemokine receptor 3 expression on activated microglia was increased 3 days after KA treatment in TNFR1 −/− mice, as measured by flow cytometry. These data suggest that TNF‐α may play a protective role through TNFR1 signaling. © 2008 Wiley‐Liss, Inc.