Abstract
The exact role of TNF-alpha 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-alpha 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-alpha may play a protective role through TNFR1 signaling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal
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Brain Injuries / chemically induced*
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Brain Injuries / genetics
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Brain Injuries / pathology
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Brain Injuries / physiopathology
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CD11b Antigen / metabolism
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Case-Control Studies
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Exploratory Behavior / drug effects
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Exploratory Behavior / physiology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / pathology*
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Kainic Acid*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Microglia / drug effects
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Microglia / metabolism
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Motor Activity / drug effects
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Motor Activity / genetics
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Neurodegenerative Diseases / chemically induced
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Neurodegenerative Diseases / genetics
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Neurodegenerative Diseases / physiopathology
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Receptors, Tumor Necrosis Factor, Type I / deficiency*
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Seizures / chemically induced
Substances
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CD11b Antigen
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Glial Fibrillary Acidic Protein
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Receptors, Tumor Necrosis Factor, Type I
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Kainic Acid