Slow Progressive Accumulation of Oligodendroglial Alpha-Synuclein (?-Syn) Pathology in Synthetic ?-Syn Fibril-Induced Mouse Models of Synucleinopathy.

ABSTRACT: Synucleinopathies are composed of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Alpha-synuclein (?-Syn) forms aggregates mainly in neurons in PD and DLB, while oligodendroglial ?-Syn aggregates are characteristic of MSA. Recent studies have demonstrated that injections of synthetic ?-Syn preformed fibrils (PFFs) into the brains of wild-type (WT) animals induce intraneuronal ?-Syn aggregates and the subsequent interneuronal transmission of ?-Syn aggregates. However, injections of ?-Syn PFFs or even brain lysates of patients with MSA have not been reported to induce oligodendroglial ?-Syn aggregates, raising questions about the pathogenesis of oligodendroglial ?-Syn aggregates in MSA. Here, we report that WT mice injected with mouse ?-Syn (m-?-Syn) PFFs develop neuronal ?-Syn pathology after short postinjection (PI) intervals on the scale of weeks, while oligodendroglial ?-Syn pathology emerges after longer PI intervals of several months. Abundant oligodendroglial ?-Syn pathology in white matter at later time points is reminiscent of MSA. Furthermore, comparison between young and aged mice injected with m-?-Syn PFFs revealed that PI intervals rather than aging correlate with oligodendroglial ?-Syn aggregation. These results provide novel insights into the pathological mechanisms of oligodendroglial ?-Syn aggregation in MSA.

SUBMITTER: Uemura N 

PROVIDER: S-EPMC6934438 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature