Journal
MOVEMENT DISORDERS
Volume 22, Issue 15, Pages 2196-2203Publisher
WILEY-LISS
DOI: 10.1002/mds.21671
Keywords
alpha-synuclein; multiple system atrophy; microglial activation; transgenic mouse; neurodegeneration
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Funding
- Austrian Science Fund FWF [P 19989] Funding Source: Medline
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The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha-synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of NOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons. The results suggest that oligodendroglial overexpression of a-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in MSA. Further, we detected increased toll-like receptor 4 immunoreactivity in both transgenic mice and MSA brains indicating a possible signaling pathway in MSA which needs to be further studied as a candidate target for neuroprotective interventions. (c) 2007 Movement Disorder Society.
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