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Phosphoglycerate Mutase 1 Promotes Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus by Facilitating the Phosphorylation of cAMP Response Element-Binding Protein

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Abstract

In a previous study, we observed a significant increase in phosphoglycerate mutase 1 (PGAM1) levels after pyridoxine treatment. In the present study, we investigated the effects of PGAM1 on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. We generated a Tat-PGAM1 fusion protein to cross the blood–brain barrier and neuronal plasma membrane. We administered the Tat peptide, control-PGAM1, or Tat-PGAM1 fusion protein to 8-week-old mice once a day for 3 weeks and tested novel object recognition memory. The mice were then euthanized to conduct western blot analysis for polyhistidine expression and immunohistochemical analysis for Ki67, doublecortin, and phosphorylated cAMP response element-binding protein. Mice treated with Tat peptide showed similar exploration times for familiar and new objects and the discrimination index was significantly lower in this group than in the control group. Tat-PGAM1 moderately increased the exploration time of new objects when compared to familiar objects, while the discrimination index was significantly higher in the Tat-PGAM1-treated group, but not in the control-PGAM1-treated group, when compared with the control group. Higher PGAM1 protein expression was observed in the hippocampus of Tat-PGAM1-treated mice when compared with the hippocampi of control, Tat peptide-, and control-PGAM1-treated mice, using western blot analysis. In addition, the numbers of proliferating cells and differentiated neuroblasts were significantly lower in the Tat peptide-treated group than in the control group. In contrast, the numbers of proliferating cells and differentiated neuroblasts in the dentate gyrus were higher in the Tat-PGAM1-treated group than in the control group. Administration of Tat-PGAM1 significantly facilitated the phosphorylation of cAMP response element-binding protein in the dentate gyrus. Administration of control-PGAM1 did not show any significant effects on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. These results suggest that PGAM1 plays a role in cell proliferation and neuroblast differentiation in the dentate gyrus via the phosphorylation of cAMP response element-binding protein in the hippocampus.

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Data Availability

The datasets and supporting materials generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the Promising-Pioneering Researcher Program through Seoul National University (SNU) in 2015 and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Nos. NRF-2016R1A2B4009156 and NRF-2018R1A2B6001941). In addition, this study was partially supported by the Research Institute for Veterinary Science of Seoul National University.

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  1. Hyo Young Jung and Hyun Jung Kwon are equally contributed to this article.

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea

    Hyo Young Jung, Woosuk Kim, Jong Whi Kim, Kyu Ri Hahn, Yeo Sung Yoon & In Koo Hwang

  2. Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea

    Hyun Jung Kwon & Dae Won Kim

  3. Department of Anatomy, College of Veterinary Medicine, Konkuk University, Seoul, 05030, South Korea

    Sung Min Nam

  4. Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam, 31151, South Korea

    Dae Young Yoo

  5. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 24341, South Korea

    Moo-Ho Won

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Contributions

HYJ, HJK, WK, SMN, JWK, KRH, DYY, MHW, YSY, DWK, and IKH conceived the study. HYJ, HJK, DWK, and IKH designed the study and wrote the manuscript. HYJ, WK, JWK, and KRH conducted the animal experiments and HJK and DWK conducted biochemical experiments. SMN, DYY, MHW, and YSY participated in designing and critical discussing the study. All authors have read and approved the final manuscript.

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Correspondence to Dae Won Kim or In Koo Hwang.

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Jung, H.Y., Kwon, H.J., Kim, W. et al. Phosphoglycerate Mutase 1 Promotes Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus by Facilitating the Phosphorylation of cAMP Response Element-Binding Protein. Neurochem Res 44, 323–332 (2019). https://doi.org/10.1007/s11064-018-2678-5

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