Abstract
The murine mutant weaver (gene symbol, wv) mouse, which carries a mutation in the gene encoding the G-protein inwardly rectifying potassium channel Girk2, exhibits a diverse range of defects as a result of postnatal cell death in several different brain neuron subtypes. Loss of dopaminergic nigrostriatal neurons in the weaver, unlike cerebellar granule neuronal loss, is via a noncaspase-mediated mechanism. Here, we present data demonstrating that degeneration of midbrain dopaminergic neurons in weaver is mediated via neuroinflammation. Furthermore, in vivo administration of the anti-inflammatory agent minocycline attenuates nigrostriatal dopaminergic neurodegeneration. This has novel implications for the use of the weaver mouse as a model for Parkinson's disease, which has been associated with increased neuroinflammation.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Analysis of Variance
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Animals
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Anti-Inflammatory Agents / administration & dosage*
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Blotting, Western
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Brain Chemistry / physiology
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CD11b Antigen / metabolism
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Cells, Cultured
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Corpus Striatum / pathology
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Corpus Striatum / ultrastructure
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Dopamine / metabolism*
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Embryo, Mammalian
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Glial Fibrillary Acidic Protein / metabolism
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Histocompatibility Antigens Class I / metabolism
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Immunohistochemistry / methods
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Mice
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Mice, Neurologic Mutants
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Mice, Transgenic
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Minocycline / administration & dosage*
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Motor Activity / drug effects
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Motor Activity / physiology
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Neurodegenerative Diseases / drug therapy*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology*
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Neurodegenerative Diseases / physiopathology*
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Oligonucleotide Array Sequence Analysis / methods
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Phosphotransferases / genetics
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Silver Staining / methods
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Substantia Nigra / pathology
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Substantia Nigra / ultrastructure
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Tyrosine 3-Monooxygenase / metabolism
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beta 2-Microglobulin / metabolism
Substances
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Anti-Inflammatory Agents
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CD11b Antigen
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Cdk5r1 protein, mouse
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Glial Fibrillary Acidic Protein
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Histocompatibility Antigens Class I
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beta 2-Microglobulin
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Tyrosine 3-Monooxygenase
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Phosphotransferases
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Minocycline
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Dopamine