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Adult Neural Stem Cells (adult + neural_stem_cell)
Selected AbstractsA Novel Approach to Align Adult Neural Stem Cells on Micropatterned Conduits for Peripheral Nerve Regeneration: A Feasibility StudyARTIFICIAL ORGANS, Issue 1 2009Shan-hui Hsu Abstract There is a strong need for nerve-tissue engineering using the guide conduit and Schwann cells or neural stem cells (NSCs) with regeneration potential for injured peripheral nerves. In this study, micropatterned poly(d,l -lactide) (PLA) conduits were fabricated by microlithography and solvent-casting. The PLA conduits were seeded with the novel green fluorescent protein (GFP)-positive adult mouse NSCs obtained using the patented method of one of the authors. About 85% of the seeded NSCs were successfully aligned on the micropatterned conduits within 72 h and expressed the genes related to the production of neurotrophic factors. Gene expressions for the neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor were upregulated by the micropatterned conduits at 72 h. The micropatterned PLA conduits seeded with the aligned NSCs were used to bridge the 10-mm sciatic nerve gaps in rats and were found to facilitate nerve repair and functional recovery during a period of 6 weeks compared with the nonseeded group. This model can be used to study the role of adult NSCs in peripheral-nerve regeneration in the future. [source] Adult neural stem cells and their role in brain pathology,THE JOURNAL OF PATHOLOGY, Issue 2 2009G Yadirgi Abstract Stem cells are multipotent cells that can give rise to a differentiated progeny as well as self-renew. The balanced coordination of these two stem cell fates is essential for embryonic development and tissue homeostasis in the adult. Perturbed stem cell function contributes significantly to a variety of pathological conditions, eg impaired self-renewal capacity due to cellular senescence contributes to ageing, and degenerative diseases or impaired stem cell differentiation by oncogenic mutations contribute to cancer formation. This review focuses on the molecular mechanisms involved in regulating the normal function of neural stem cells in the adult mammalian brain and on the involvement of these cells in brain pathology. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Guanosine improves motor behavior, reduces apoptosis, and stimulates neurogenesis in rats with parkinsonismJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2009Caixin Su Abstract Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) caused by an abnormal rate of apoptosis. Endogenous stem cells in the adult mammalian brain indicate an innate potential for regeneration and possible resource for neuroregeneration in PD. We previously showed that guanosine prevents apoptosis even when administered 48 hr after the toxin 1-methyl-4-phenylpyridinium (MPP+). Here, we induced parkinsonism in rats with a proteasome inhibitor. Guanosine treatment reduced apoptosis, increased tyrosine hydroxylase,positive dopaminergic neurons and expression of tyrosine hydroxylase in the SNc, increased cellular proliferation in the SNc and subventricular zone, and ameliorated symptoms. Proliferating cells in the subventricular zone were nestin-positive adult neural progenitor/stem cells. Fibroblast growth factor-2-expressing cells were also increased by guanosine. Thus, guanosine protected cells from apoptosis and stimulated "intrinsic" adult progenitor/stem cells to become dopaminergic neurons in rats with proteasome inhibitor,induced PD. The cellular/molecular mechanisms underlying these effects may open new avenues for development of novel therapeutics for PD. © 2008 Wiley-Liss, Inc. [source] Nucleotides and epidermal growth factor induce parallel cytoskeletal rearrangements and migration in cultured adult murine neural stem cellsACTA PHYSIOLOGICA, Issue 2 2010I. Grimm Abstract Aim:, The adult subventricular zone (SVZ) contains neural stem cells that generate neuroblasts migrating to the olfactory bulb (OB) and differentiating into interneurones. The molecular cues controlling essential functions within the neurogenesis pathway such as proliferation, short and long distance migration, functional integration and cell survival are poorly understood. We have previously shown that cultured adult neural stem cells express a considerable variety of nucleotide receptors and that nucleotides and epidermal growth factor (EGF) induce converging intracellular signalling pathways that carry potential for synergism in the control of neural stem cell proliferation and cell survival. Here we investigate the role of EGF and the nucleotides ATP, ADP,S and UTP in neural stem cell migration. Methods:, Neural stem cells were prepared from adult mice and subjected to adherent culture. Labelling of F-actin was performed with tetramethylrhodamine isothiocyanate-phalloidin. Images were processed for quantitative evaluation of fluorescence labelling. Agonist-induced phosphorylation of AKT and focal adhesion kinase was analysed by quantitative Western blotting. Agonist-dependent cell migration was assayed using 48-well microchemotaxis chambers. Results:, Nucleotides and EGF induce the formation of stress fibres, an increase in the cortical actin cytoskeleton and in cell spreading. This is associated with increased phosphorylation of AKT and focal adhesion kinase. Using microchemotaxis chambers we demonstrate a parallel increase in cell migration. Conclusion:, Our results suggest that nucleotides and EGF acting as paracrine or autocrine signalling substances can be of relevance for structuring and maintaining the cytoarchitecture of the SVZ and the stream of neuroblasts migrating to the OB. [source] Evidence for neural stem cells in the medaka optic tectum proliferation zones,DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2010Alessandro Alunni Abstract Few adult neural stem cells have been characterized in vertebrates. Although teleosts continually generate new neurons in many regions of the brain after embryogenesis, only two types of neural stem cells (NSCs) have been reported in zebrafish: glial cells in the forebrain resembling mammalian NSCs, and neuroepithelial cells in the cerebellum. Here, following our previous studies on dividing progenitors (Nguyen et al. [1999]: J Comp Neurol 413:385,404.), we further evidenced NSCs in the optic tectum (OT) of juvenile and adult in the medaka, Oryzias latipes. To detect very slowly cycling progenitors, we did not use the commonly used BrdU/PCNA protocol, in which PCNA may not be present during a transiently quiescent state. Instead, we report the optimizations of several protocols involving long subsequent incubations with two thymidine analogs (IdU and CldU) interspaced with long chase times between incubations. These protocols allowed us to discriminate and localize fast and slow cycling cells in OT of juvenile and adult in the medaka. Furthermore, we showed that adult OT progenitors are not glia, as they express neither brain lipid-binding protein (BLBP) nor glial fibrillary acidic protein (GFAP). We also showed that expression of pluripotency-associated markers (Sox2, Musashi1 and Bmi1) colocalized with OT progenitors. Finally, we described the spatio-temporally ordered population of NSCs and progenitors in the medaka OT. Hence, the medaka appears as an invaluable model for studying neural progenitors that will open the way to further exciting comparative studies of neural stem cells in vertebrates. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 693,713, 2010 [source] Expression of Sox11 in adult neurogenic niches suggests a stage-specific role in adult neurogenesisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2009Anja Haslinger Abstract In the mammalian brain, neural stem and progenitor cells in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus generate new neurons throughout adulthood. The generation of new functional neurons is a complex process that is tightly controlled by extrinsic signals and that is characterized by stage-specific gene expression programs and cell biological processes. The transcription factors regulating such stage-specific developmental steps in adult neurogenesis are largely unknown. Here we report that Sox11, a member of the group C Sox transcription factor family, is prominently expressed in the neurogenic areas of the adult brain. Further analysis revealed that Sox11 expression is strictly confined to doublecortin-expressing neuronally committed precursors and immature neurons but that Sox11 is not expressed in non-committed Sox2-expressing precursor cells and mature neurons of the adult neurogenic lineage. Finally, overexpression of Sox11 promotes the generation of doublecortin-positive immature neurons from adult neural stem cells in vitro. These data indicate that Sox11 is involved in the transcriptional regulation of specific gene expression programs in adult neurogenesis at the stage of the immature neuron. [source] Anatomical perspectives on adult neural stem cellsJOURNAL OF ANATOMY, Issue 3 2005C. Watts Abstract The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies. [source] Effects of the monomeric, oligomeric, and fibrillar A,42 peptides on the proliferation and differentiation of adult neural stem cells from subventricular zoneJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Chaejeong Heo Abstract The incidence of amyloid plaques, composed mainly of ,-amyloid peptides (A,), does not correlate well with the severity of neurodegeneration in patients with Alzheimer's disease (AD). The effects of A,42 on neurons or neural stem cells (NSCs) in terms of the aggregated form remain controversial. We prepared three forms of oligomeric, fibrillar, and monomeric A,42 peptides and investigated their effects on the proliferation and neural differentiation of adult NSCs, according to the degree of aggregation or concentration. A low micromolar concentration (1 ,mol/L) of oligomeric A,42 increased the proliferation of adult NSCs remarkably in a neurosphere assay. It also enhanced the neuronal differentiation of adult NSCs and their ability to migrate. These results provide us with valuable information regarding the effects of A,42 on NSCs in the brains of patients with AD. [source] Amphiregulin is a mitogen for adult neural stem cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2002Anna Falk Abstract Neurons are continuously generated from stem cells in the hippocampus and along the lateral ventricles in the adult brain. Neural stem cells can be propagated in vitro in the presence of epidermal growth factor (EGF) or fibroblast growth factor-2. We report here that amphiregulin, a growth factor related to EGF, is a mitogen for adult mouse neural stem cells in vitro and displays potency similar to that of EGF. Neural stem cell cultures can be initiated and the cells propagated as efficiently in the presence of amphiregulin only as with EGF. Furthermore, we show that amphiregulin is expressed in the choroid plexus of the ventricular system and in the hippocampus in the adult brain, suggesting that amphiregulin may participate in the regulation of neural stem cell proliferation and neurogenesis in the adult brain. © 2002 Wiley-Liss, Inc. [source] Small potent ligands to the insulin-regulated aminopeptidase (IRAP)/AT4 receptorJOURNAL OF PEPTIDE SCIENCE, Issue 7 2007Andreas Axén Abstract Angiotensin IV analogs encompassing aromatic scaffolds replacing parts of the backbone of angiotensin IV have been synthesized and evaluated in biological assays. Several of the ligands displayed high affinities to the insulin-regulated aminopeptidase (IRAP)/AT4 receptor. Displacement of the C -terminal of angiotensin IV with an o -substituted aryl acetic acid derivative delivered the ligand 4, which exhibited the highest binding affinity (Ki = 1.9 nM). The high affinity of this ligand provides support to the hypothesis that angiotensin IV adopts a ,-turn in the C -terminal of its bioactive conformation. Ligand (4) inhibits both human IRAP and aminopeptidase N-activity and induces proliferation of adult neural stem cells at low concentrations. Furthermore, ligand 4 is degraded considerably more slowly in membrane preparations than angiotensin IV. Hence, it might constitute a suitable research tool for biological studies of the (IRAP)/AT4 receptor. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [source] | |||||||||||||