Literatura académica sobre el tema "Meninges, neural stem cells, postnatal neurogenesis"

Stem cells of the central nervous system have received a great deal of attention in neurobiology in the last decade. It has been shown that neurogenesis occurs in the postnatal period in specialized niches of the adult mammalian brain. The niche is a key regulator of stem cell behavior. Recent data underscore the complexity and heterogeneity of the different components of the niche, and the presence of local signaling microdomain. The review is devoted to recent views on the structural organization of neurogenic niches and regulatory factors involved at different stages of neurogenesis in the postnatal period. Understanding of stem cells behavior in the niches can serve as a basis for determination of these cells function in the adult brain.

Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.

Endogenous DNA double-strand breaks (DSBs) formation and repair in neural stem/progenitor cells (NSPCs) play fundamental roles in neurogenesis and neurodevelopmental disorders. NSPCs exhibit heterogeneity in terms of lineage fates and neurogenesis activity. Whether NSPCs also have heterogeneous regulations on DSB formation and repair to accommodate region-specific neurogenesis has not been explored. Here, we identified a regional regulator Filia, which is predominantly expressed in mouse hippocampal NSPCs after birth and regulates DNA DSB formation and repair. On one hand, Filia protects stalling replication forks and prevents the replication stress-associated DNA DSB formation. On the other hand, Filia facilitates the homologous recombination–mediated DNA DSB repair. Consequently, Filia−/− mice had impaired hippocampal NSPC proliferation and neurogenesis and were deficient in learning, memory, and mood regulations. Thus, our study provided the first proof of concept demonstrating the region-specific regulations of DSB formation and repair in subtypes of NSPCs.

Two main stem cell pools exist in the postnatal mammalian brain that, although they share some “stemness” properties, also exhibit significant differences. Multipotent neural stem cells survive within specialized microenvironments, called niches, and they are vulnerable to ageing. Oligodendroglial lineage-restricted progenitor cells are widely distributed in the brain parenchyma and are more resistant to the effects of ageing. Here, we create polymorphic neural stem cell cultures and allow cells to progress towards the neuronal and the oligodendroglial lineage. We show that the divergence of cell fate is accompanied by a divergence in the properties of progenitors, which reflects their adaptation to life in the niche or the parenchyma. Neurogenesis shows significant spatial restrictions and a dependence on laminin, a major niche component, while oligodendrogenesis shows none of these constraints. Furthermore, the blocking of integrin-β1 leads to opposing effects, reducing neurogenesis and enhancing oligodendrogenesis. Therefore, polymorphic neural stem cell assays can be used to investigate the divergence of postnatal brain stem cells and also to predict the in vivo effects of potential therapeutic molecules targeting stem and progenitor cells, as we do for the microneurotrophin BNN-20.