Search results for "Neural Stem Cell"
showing 10 items of 250 documents
Dynamic Changes in the Neurogenic Potential in the Ventricular–Subventricular Zone of Common Marmoset during Postnatal Brain Development
2020
AbstractEven after birth, neuronal production continues in the ventricular–subventricular zone (V–SVZ) and hippocampus in many mammals. The immature new neurons (“neuroblasts”) migrate and then mature at their final destination. In humans, neuroblast production and migration toward the neocortex and the olfactory bulb (OB) occur actively only for a few months after birth and then sharply decline with age. However, the precise spatiotemporal profiles and fates of postnatally born neurons remain unclear due to methodological limitations. We previously found that common marmosets, small nonhuman primates, share many features of V–SVZ organization with humans. Here, using marmosets injected wit…
Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells
2018
Abstract: In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngb(fl)-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (Ngb(KO)-)NSC line. Ngb(KO)-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upr…
Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural stem cell maintenance.
2013
Relative quiescence and self renewal are defining features of adult stem cells, but their potential coordination remains unclear. Subependymal neural stem cells (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit rapid expansion that is followed by their permanent loss later in life. Here we demonstrate that transcription of the gene encoding bone morphogenetic protein 2 (Bmp2) in NSCs is under the direct negative control of p21 through actions that are independent of CDK. Loss of p21 in NSCs results in increased levels of secreted BMP2, which induce premature terminal differentiation of multipotent NSCs into mature non-neurogenic astrocytes in an autocrine and/or …
Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression.
2012
Summary In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulate…
The APC/C cofactor Cdh1 prevents replicative stress and p53-dependent cell death in neural progenitors
2013
The E3-ubiquitin ligase APC/C-Cdh1 is essential for endoreduplication but its relevance in the mammalian mitotic cell cycle is still unclear. Here we show that genetic ablation of Cdh1 in the developing nervous system results in hypoplastic brain and hydrocephalus. These defects correlate with enhanced levels of Cdh1 substrates and increased entry into the S phase in neural progenitors. However, cell division is prevented in the absence of Cdh1 due to hyperactivation of cyclin-dependent kinases, replicative stress, induction of p53, G2 arrest and apoptotic death of these progenitor cells. Concomitant ablation of p53 rescues apoptosis but not replicative stress, resulting in the presence of …
Dual roles of Aβ in proliferative processes in an amyloidogenic model of Alzheimer’s disease
2017
Alzheimer’s disease is a major neurodegenerative disorder that leads to severe cognitive deficits in the elderly population. Over the past two decades, multiple studies have focused on elucidating the causative factors underlying memory defects in Alzheimer’s patients. In this regard, new evidence linking Alzheimer’s disease-related pathology and neuronal stem cells suggests that hippocampal neurogenesis impairment is an important factor underlying these cognitive deficits. However, because of conflicting results, the impact of Aβ pathology on neurogenesis/gliogenesis remains unclear. Here, we investigated the effect of Aβ on neuronal and glial proliferation by using an APP/PS1 transgenic m…
Peroxisome proliferator-activated receptor γ ligands regulate neural stem cell proliferation and differentiation in vitro and in vivo.
2011
Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors and its ligands are known to control many physiological and pathological situations. Its role in the central nervous system has been under intense analysis during the last years. Here we show a novel function for PPARγ in controlling stem cell expansion in the adult mammalian brain. Adult rats treated with pioglitazone, a specific ligand of PPARγ, had elevated numbers of proliferating progenitor cells in the subventricular zone and the rostral migratory stream. Electron microscopy analysis also showed important changes in the subventricular zone ultrastructure of pioglitazone-t…
Functional Integration of Neuronal Precursors in the Adult Murine Piriform Cortex
2018
Abstract The extent of functional maturation and integration of nonproliferative neuronal precursors, becoming neurons in the adult murine piriform cortex, is largely unexplored. We thus questioned whether precursors eventually become equivalent to neighboring principal neurons or whether they represent a novel functional network element. Adult brain neuronal precursors and immature neurons (complex cells) were labeled in transgenic mice (DCX-DsRed and DCX-CreERT2 /flox-EGFP), and their cell fate was characterized with patch clamp experiments and morphometric analysis of axon initial segments. Young (DCX+) complex cells in the piriform cortex of 2- to 4-month-old mice received sparse synapt…
Human adult periodontal ligament-derived cells integrate and differentiate after implantation into the adult mammalian brain.
2013
Previous studies suggest that neural crest (NC)-derived stem cells may reside in NC derivatives including the human periodontal ligament (hPDL). The isolation and manipulation of autologous NC-derived cells could be an accessible source of adult neural stem cells for their use in cell replacement and gene transfer to the diseased central nervous system. In this study, we examined the expression of NC markers and neural differentiation potential of hPDL-derived cells both in vitro and in vivo. In vitro we found that hPDL-derived cells expressed stem cell markers (Oct3/4, Nestin, Sox2, and Musashi-1) and a subset of NC cell markers (Slug, p75(NTR), Twist, and Sox9). hPDL-derived cells differe…
Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain
2006
Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating PSA-NCAM(+) and Doublecortin(+) neural precursors within the …