Transcriptional dysregulation in the cerebellum triggered by oligodendroglial α-synucleinopathy: insights from a transgenic mouse into the early disease mechanisms of MSA

• DOI: 10.1007/s00702-025-02892-5
• Publication Date: 2025-02-15T12:06:12Z
• Authors: Antonio Heras-Garvin; Lisa Fellner; Roberta Granata; Gregor K. Wenning; Nadia Stefanova

Abstract Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by abnormal accumulation of α-synuclein, progressive neuronal loss, motor impairment and widespread pathological changes, which include significant involvement the cerebellum. To understand early molecular mechanisms that might underlie α-synuclein-triggered MSA cerebellar pathology, we performed RNA sequencing (RNA-Seq) samples from well-established model MSA. RNA-Seq differential gene expression analysis was conducted in PLP-αSyn Cerebellum two 12-month-old wildtype mice were used. Gene ontology (GO) KEGG enrichment analyses differentially expressed genes (DEGs) to explore processes involved MSA-like disease progression. The overlap between transcriptional changes those associated with aging also evaluated. demonstrated dysregulation cerebellum mice, even at stages. GO DEGs point potential role synaptic dysfunction, cellular signaling inflammation pathology mice. In addition, exacerbate Additionally, our both control showed age-related mid-aged controls seem be present young Thus, lead an acceleration aging-related mechanisms. Our findings demonstrate triggered oligodendroglial α-synucleinopathy revealing pathways critical for MSA, may serve as targets therapeutic interventions this devastating disorder.