#Repository accompanying 'Metabolic perturbation in ependymal cells leads to local and distant neurodegeneration with cognitive decline'
Single cell dataset can be visualized at our Ependymal atlas (http://www.biernaskielab.ca/ECellAtlas)
Ependymal cells (ECs) are specialized multi-ciliated glial cells that line the ventricular system of the brain, regulating cerebrospinal fluid (CSF) flow and the neighbouring neural stem cell (NSC) niche. However, their role in maintaining brain homeostasis or in disease pathogenesis remains unclear. To elucidate their function, we disrupted ependymal glucose metabolism by genetically deleting glucose-transporter-1 (GLUT1) in postnatal ECs. This resulted in CSF flow changes, disrupted NSC differentiation, and reduced neuroblast migration. These mice also exhibited periventricular lipid droplet accumulation, reminiscent of Alzheimer’s disease pathology. Aged conditional KO mice exhibited progressive cognitive and motor dysfunction, and onset of seizure activity. These behavioral deficits were accompanied by various neurodegenerative pathologies, including dysmyelination, microglia-associated inflammation, and lipid imbalance. Furthermore, 5xFAD mice combined with EC metabolic perturbation exhibited accelerated disease onset. These findings suggest that ECs are important regulators of brain homeostasis, and their dysfunction may contribute to the pathogenesis of neurodegenerative diseases.
- Ependymal metabolic perturbation triggers lipid accumulation locally and in distant brain regions
- Ependymal dysfunction disrupts cerebrospinal fluid flow and neurogenesis.
- Ependymal perturbation leads to cognitive decline and seizure activity.
- Ependymal dysfunction triggers progressive dysmyelination, neurodegeneration, and neuroinflammation.
- Ependymal dysfunction exacerbates disease onset in an AD mouse model.
scRNA-Seq datasets characterizing changes within the SVZ niche following ependymal dysfunction at 6 months and 12 months
NCBI GEO: [GSE255150]