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- Xu, G., et al.
(author)
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Functional analysis of platelet-derived growth factor receptor-β in neural stem/progenitor cells
- 2013
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In: Neuroscience. - : Elsevier BV. - 0306-4522. ; 238, s. 195-208
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Journal article (peer-reviewed)abstract
- Activation of neural stem/progenitor cells (NSPCs) is a potential therapeutic strategy of neurological disorders. In this study, NSPCs of subventricular zone were isolated and cultured from platelet-derived growth factor-β-receptor-knockout (PDGFR-β−/−) mice of postnatal day 1 (P1) and P28, and the roles of PDGFR-β were examined in these cells. In PDGFR-β-preserving control NSPCs, stem cell activities, such as numbers and diameters of secondary neurospheres, cell proliferation and survival rates, were significantly higher in P1 NSPCs than those in P28 NSPCs. In PDGFR-β−/− NSPCs, most of these parameters were decreased as compared with age-matched controls. Among them, the decrease of secondary neurosphere formation was most striking in P1 and P28 PDGFR-β−/− NSPCs and in P28 control NSPCs as compared with P1 control NSPCs. PCR-array and following quantitative real-time PCR (qRT-PCR) analyses demonstrated that expressions of fibroblast growth factor-2 (FGF2) and exons IV–IX of brain-derived neurotrophic factor (BDNF) were decreased, and noggin was increased in P1 PDGFR-β−/− as compared with P1 controls. Addition of BDNF rescued the number and diameter of secondary neurospheres in P1 PDGFR-β−/− NSPCs to similar levels as controls. The expressions of PDGFs and PDGFRs in control NSPCs were increased along with the differentiation-induction, where phosphorylated PDGFR-β was co-localized with neuronal and astrocyte differentiation markers. In controls, the neuronal differentiation was decreased, and the glial differentiation was increased from P1 to P28 NSPCs. Compared with P1 controls, neuronal differentiation was reduced in P1 PDGFR-β−/− NSPCs, whereas glial differentiation was comparable between the two genotypes. These results suggest that PDGFR-β signaling is important for the self-renewal and multipotency of NSPCs, particularly in neonatal NSPCs. BDNF, FGF2, and noggin may be involved in the effects of PDGFR-β signaling in these cells. Accordingly, the activation of PDGFR-β in NSPCs may be a novel therapeutic strategy of neurological diseases.
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- Funa, Keiko, 1949, et al.
(author)
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The Roles of PDGF in Development and During Neurogenesis in the Normal and Diseased Nervous System
- 2014
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In: Journal of Neuroimmune Pharmacology. - : Springer Science and Business Media LLC. - 1557-1890 .- 1557-1904. ; 9:2, s. 168-181
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Research review (peer-reviewed)abstract
- The four platelet-derived growth factor (PDGF) ligands and PDGF receptors (PDGFRs), alpha and beta (PDGFRA, PDGFRB), are essential proteins that are expressed during embryonic and mature nervous systems, i.e., in neural progenitors, neurons, astrocytes, oligodendrocytes, and vascular cells. PDGF exerts essential roles from the gastrulation period to adult neuronal maintenance by contributing to the regulation of development of preplacodal progenitors, placodal ectoderm, and neural crest cells to adult neural progenitors, in coordinating with other factors. In adulthood, PDGF plays critical roles for maintenance of many specific cell types in the nervous system together with vascular cells through controlling the blood brain barrier homeostasis. At injury or various stresses, PDGF modulates neuronal excitability through adjusting various ion channels, and affecting synaptic plasticity and function. Furthermore, PDGF stimulates survival signals, majorly PI3-K/Akt pathway but also other ways, rescuing cells from apoptosis. Studies imply an involvement of PDGF in dendrite spine morphology, being critical for memory in the developing brain. Recent studies suggest association of PDGF genes with neuropsychiatric disorders. In this review, we will describe the roles of PDGF in the nervous system, from the discovery to recent findings, in order to understand the broad spectrum of PDGF in the nervous system. Recent development of pharmacological and replacement therapies targeting the PDGF system is discussed.
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