Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy - PubMed
5 hours ago
- #multiple system atrophy
- #microglia dysfunction
- #single-nucleus transcriptomics
- Single-nucleus RNA sequencing of postmortem striatal tissue from MSA, PD, and non-neurological cases revealed significant differences in astroglia and microglia subtypes, but not in oligodendroglia or neurons.
- PD brains showed abundant proinflammatory microglia expressing MHC class II HLA haplotypes and more homeostatic astrocytes, whereas MSA lacked activated microglia but had more reactive astrocytes.
- Transcriptomic analysis suggested compromised oligodendrocyte signaling in MSA, with microglia in a state of immune tolerance or exhaustion.
- Microglia derived from iPSC exposed to patient cerebrospinal fluid exhibited reduced phagocytic activity, particularly in MSA, indicating a dysfunctional immune response potentially contributing to MSA's severe pathophysiology.