Microglial activation mediates neurodegeneration related to oligodendroglial α‐synucleinopathy: Implications for multiple system atrophy

N Stefanova, M Reindl, M Neumann… - … : official journal of the …, 2007 - Wiley Online Library
Movement disorders: official journal of the Movement Disorder Society, 2007Wiley Online Library
The role of microglial activation in multiple system atrophy (MSA) was investigated in a
transgenic mouse model featuring oligodendroglial α‐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 iNOS and correlating with
dopaminergic neuronal loss. Suppression of microglial activation by early long‐term …
Abstract
The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial α‐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 iNOS 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 α‐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. © 2007 Movement Disorder Society
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