Search

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 (p75 NTR-/- ) in mice reduced SVZ NSPC migration towards the lesion area after cortical injury and that p75 NTR-/- NSPCs failed to migrate upon BDNF stimulation in vitro. Cortical injury rapidly increased p75 NTR abundance in SVZ NSPCs via bone morphogenetic protein (BMP) receptor signaling. SVZ-derived p75 NTR-/- NSPCs revealed an altered cytoskeletal network- and small GTPase family-related gene and protein expression. In accordance, BMP-treated non-migrating p75 NTR-/- NSPCs revealed an altered morphology and α-tubulin expression compared to BMP-treated migrating wild-type NSPCs. We propose that BMP-induced p75 NTR abundance in NSPCs is a regulator of SVZ NSPC migration to the lesion area via regulation of the cytoskeleton following cortical injury., (© 2021. The Author(s).)

Neural stem/progenitor cells (NSPCs) are found in the adult brain and spinal cord, and endogenous or transplanted NSPCs contribute to repair processes and regulate immune responses in the CNS. However, the molecular mechanisms of NSPC survival and integration as well as their fate determination and functionality are still poorly understood. Inhibitor of DNA binding (Id) proteins are increasingly recognized as key determinants of NSPC fate specification. Id proteins act by antagonizing the DNA-binding activity of basic helix-loop-helix (bHLH) transcription factors, and the balance of Id and bHLH proteins determines cell fate decisions in numerous cell types and developmental stages. Id proteins are central in responses to environmental changes, as they occur in CNS injury and disease, and cellular responses in adult NSPCs implicate Id proteins as prime candidates for manipulating stemcell behavior. Here, we outline recent advances in understanding Id protein pleiotropic functions in CNS diseases and propose an integrated view of Id proteins and their promise as potential targets in modifying stemcell behavior to ameliorate CNS disease., (© 2021. The Author(s).)

The brain function depends on a continuous supply of blood. The blood-brain barrier (BBB), which is formed by vascular cells and glia, separates components of the circulating blood from neurons and maintains the precisely regulated brain milieu required for proper neuronal function. A compromised BBB alters the transport of molecules between the blood and brain and has been associated with or shown to precede neurodegenerative disease. Blood components immediately leak into the brain after mechanical damage or as a consequence of a compromised BBB in brain disease changing the extracellular environment at sites of vascular damage. It is intriguing how blood-derived components alter the cellular and molecular constituents of the neurovascular interface after BBB opening. We recently identified an unexpected role for the blood protein fibrinogen, which is deposited in the nervous system promptly after vascular damage, as an initial scar inducer by promoting the availability of active TGF-β. Fibrinogen-bound latent TGF-β interacts with astrocytes, leading to active TGF-β formation and activation of the TGF-β/Smad signaling pathway. Here, we discuss the pleiotropic effects of potentially vascular-derived TGF-β on cells at the neurovascular interface and we speculate how these biological effects might contribute to degeneration and regeneration processes. Summarizing the effects of the components derived from the brain vascular system on nervous system regeneration might support the development of new therapeutic approaches.