title: Temporal changes in the response of SVZ neural stem cells to intraventricular administration of growth factors.
abstract: In vivo growth factor (GF) treatment is a promising approach to enhance the regenerative capacity of neural stem cells (NSCs) for brain repair. However, how exogenous GFs affect endogenous NSCs is not well understood. This study investigated the impact of intraventricular administration of fibroblast growth factor 2 and epidermal growth factor on NSCs in the subventricular zone of intact adult mice. GFs were administered for various periods (3, 7, 10, and 14 days), and the proliferation and neuronal production of NSCs were assessed during and after GF treatment. We found that proliferation of NSCs and their progeny is markedly augmented during the first 7 days after the initiation of GF treatment. GF treatment for longer periods, however, did not lead to further increases in the NSC pool, but rather attenuated such proliferation and inhibited neurogenesis. As a result, the production of new olfactory bulb neurons was increased in animals treated with GFs for 7 days but decreased in animals treated for 14 days. These results show time-dependent changes in the response of NSCs to exogenous GFs and demonstrate that precise control of the duration of GF treatment is important for significant enhancement of neuronal production by NSCs in vivo for brain repair.
authors: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan; Department of Cellular Neurobiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan.
authors: Takashi
authors: T
authors: Ochi
authors: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. Electronic address: hnakatomi-tky@umin.ac.jp.
authors: Hirofumi
authors: H
authors: Nakatomi
authors: Department of Neurosurgery, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8606, Japan.
authors: Akihiro
authors: A
authors: Ito
authors: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Hideaki
authors: H
authors: Imai
authors: Department of Cellular Neurobiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8654, Japan.
authors: Shigeo
authors: S
authors: Okabe
authors: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Nobuhito
authors: N
authors: Saito
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015222:Sodium Channels; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C084016:GFLN1 protein, Loligo opalescens; D005904:Glial Fibrillary Acidic Protein; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C518597:Par6 protein, mouse; D055748:SOXB1 Transcription Factors; D015222:Sodium Channels; C527783:Sox2 protein, mouse; D014404:Tubulin; C462941:beta3 tubulin, mouse; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine
keywords: Brain repair; Growth factors; Neural stem cells; Regeneration; Subventricular zone