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Pyridoxine Enhances Cell Proliferation and Neuroblast Differentiation by Upregulating the GABAergic System in the Mouse Dentate Gyrus

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Abstract

We investigated the effects of pyridoxine (vitamin B6) on cell death, cell proliferation, neuroblast differentiation, and the GABAergic system in the mouse dentate gyrus. We administered pyridoxine (350 mg/kg intraperitoneally) to 8 week old mice twice a day for 14 days and sacrificed them at 10 weeks of age. Pyridoxine treatment did not induce neuronal death or activate microglia in the dentate gyrus, while glial fibrillary acidic protein (GFAP)-positive cells were significantly increased in the subgranular zone of the dentate gyrus. The increase in GFAP-positive cells was confirmed to be due to proliferating cells based on double immunofluorescence staining. GFAP-positive cells, which were also labeled with Ki67, a marker for cell proliferation, and doublecortin, a marker for neuroblast differentiation, were significantly increased in the pyridoxine-treated group compared to those in the vehicle-treated group. Pyridoxine treatment also increased the protein levels of glutamic acid decarboxylase (GAD) 67, an enzyme for GABA synthesis, and pyridoxal 5′-phosphate (PNP) oxidase, an enzyme for pyridoxal phosphate synthesis, in the dentate gyrus. These results suggest that pyridoxine treatment distinctly increases cell proliferation, neuroblast differentiation, and upregulated the GABAergic system, as revealed by the increases of GAD67 and PNP oxidase in the mouse dentate gyrus.

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Acknowledgments

The authors would like to thank Mr. Seung Uk Lee and Mrs. Hyun Sook Kim for their technical help in this study, and Seung-Hae Kwon of the Korean Basic Science Institute Chuncheon Center for technical assistance with the confocal image analyses (LSM 510 META NLO). This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST), Republic of Korea (2010-0007711).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Dae Young Yoo, Woosuk Kim, Yeo Sung Yoon & In Koo Hwang

  2. Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 200-702, South Korea

    Dae Won Kim & Soo Young Choi

  3. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Ki-Yeon Yoo & Moo-Ho Won

  4. Department of Veterinary Internal Medicine, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Jin Young Chung & Hwa Young Youn

  5. Department of Neurology, Seoul National University Hospital, Seoul, 110-744, South Korea

    Jin Young Chung

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  1. Dae Young Yoo
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  2. Woosuk Kim
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Correspondence to Moo-Ho Won or In Koo Hwang.

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11064_2010_385_MOESM1_ESM.tif

sFig. 1. Micrographs of doublecortin (DCX) immunoreactive neuroblasts without (A) and with (B) tertiary dendrites. (TIFF 443 kb)

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Yoo, D.Y., Kim, W., Kim, D.W. et al. Pyridoxine Enhances Cell Proliferation and Neuroblast Differentiation by Upregulating the GABAergic System in the Mouse Dentate Gyrus. Neurochem Res 36, 713–721 (2011). https://doi.org/10.1007/s11064-010-0385-y

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