P75 neurotrophin receptor controls subventricular zone neural stem cell migration after stroke.
Sachin S DeshpandeSubash C MalikPasquale ConfortiJia-di LinYu-Hsuan ChuSuvra NathFranziska GreulichMeike-Ast DumbachN Henriette UhlenhautChristian SchachtrupPublished in: Cell and tissue research (2021)
Stroke is the leading cause of adult disability. Endogenous neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to the brain repair process. However, molecular mechanisms underlying CNS disease-induced SVZ NSPC-redirected migration to the lesion area are poorly understood. Here, we show that genetic depletion of the p75 neurotrophin receptor (p75NTR-/-) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75NTR-/- NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75NTR-/- NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75NTR-/- NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury.
Keyphrases
- mesenchymal stem cells
- cell migration
- wild type
- high glucose
- bone regeneration
- diabetic rats
- drug induced
- poor prognosis
- copy number
- single cell
- atrial fibrillation
- binding protein
- white matter
- type diabetes
- adipose tissue
- endothelial cells
- transcription factor
- cerebral ischemia
- microbial community
- oxidative stress
- wastewater treatment
- genome wide identification
- childhood cancer