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The Journal of Neuroscience, November 8, 2006, 26(45):11644-11651; doi:10.1523/JNEUROSCI.3447-06.2006

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Development/Plasticity/Repair
Nigrostriatal Dopaminergic Neurodegeneration in the Weaver Mouse Is Mediated via Neuroinflammation and Alleviated by Minocycline Administration

Jun Peng,1 Lin Xie,1 Fang Feng Stevenson,1 Simon Melov,1 Donato A. Di Monte,2 and Julie K. Andersen1

1Buck Institute for Age Research, Novato, California 94945, and 2Parkinson's Institute, Sunnyvale, California 94089

Correspondence should be addressed to Julie K. Andersen, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945. Email: jandersen{at}buckinstitute.org

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.

Key words: weaver; dopaminergic midbrain neurons; caspase-independent cell death; microglial activation; minocycline; Parkinson

Received April 30, 2006; revised Sept. 21, 2006; accepted Sept. 22, 2006.

Correspondence should be addressed to Julie K. Andersen, Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945. Email: jandersen{at}buckinstitute.org




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[Abstract] [Full Text] [PDF]


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