Nigrostriatal Dopaminergic Neurodegeneration in theWeaverMouse Is Mediated via Neuroinflammation and Alleviated by Minocycline Administration

Abstract

The murine mutantweaver(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 theweaver, unlike cerebellar granule neuronal loss, is via a noncaspase-mediated mechanism. Here, we present data demonstrating that degeneration of midbrain dopaminergic neurons inweaveris mediated via neuroinflammation. Furthermore,in vivoadministration of the anti-inflammatory agent minocycline attenuates nigrostriatal dopaminergic neurodegeneration. This has novel implications for the use of theweavermouse as a model for Parkinson's disease, which has been associated with increased neuroinflammation.