Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration.
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.
Peng
Jun
J
Buck Institute for Age Research, Novato, California 94945, USA.
Xie
Lin
L
Stevenson
Fang Feng
FF
Melov
Simon
S
Di Monte
Donato A
DA
Andersen
Julie K
JK
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000473:pathology / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008911:Minocycline / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010770:Phosphotransferases / Q000235:genetics; D016622:Silver Staining / Q000379:methods; D013378:Substantia Nigra / Q000473:pathology / Q000648:ultrastructure; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; C492236:Cdk5r1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D014446:Tyrosine 3-Monooxygenase; D010770:Phosphotransferases; D008911:Minocycline; D004298:Dopamine