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Neurochemical Research

, Volume 44, Issue 2, pp 374–387 | Cite as

Impaired Cerebellar Development in Mice Overexpressing VGF

  • Takahiro Mizoguchi
  • Masamitsu Shimazawa
  • Kazuki Ohuchi
  • Yoshiki Kuse
  • Shinsuke Nakamura
  • Hideaki HaraEmail author
Original Paper

Abstract

VGF nerve growth factor inducible (VGF) is a neuropeptide precursor induced by brain-derived neurotrophic factor and nerve growth factor. VGF is increased in the prefrontal cortex and cerebrospinal fluid in schizophrenia patients. In our previous study, VGF-overexpressing mice exhibited schizophrenia-like behaviors and smaller brain weights. Brain developmental abnormality is one cause of mental illness. Research on brain development is important for discovery of pathogenesis of mental disorders. In the present study, we investigated the role of VGF on cerebellar development. We performed a histological analysis with cerebellar sections of adult and postnatal day 3 mice by Nissl staining. To investigate cerebellar development, we performed immunostaining with antibodies of immature and mature granule cell markers. To understand the mechanism underlying these histological changes, we examined MAPK, Wnt, and sonic hedgehog signaling by Western blot. Finally, we performed rotarod and footprint tests using adult mice to investigate motor function. VGF-overexpressing adult mice exhibited smaller cerebellar sagittal section area. In postnatal day 3 mice, a cerebellar sagittal section area reduction of the whole cerebellum and external granule layer and a decrease in the number of mature granule cells were found in VGF-overexpressing mice. Additionally, the number of proliferative granule cell precursors was lower in VGF-overexpressing mice. Phosphorylation of Trk and Erk1 were increased in the cerebellum of postnatal day 3 VGF-overexpressing mice. Adult VGF-overexpressing mice exhibited motor disability. All together, these findings implicate VGF in the development of cerebellar granule cells via promoting MAPK signaling and motor function in the adult stage.

Keywords

VGF nerve growth factor inducible Neural development Cerebellum Granule cell Motor coordination 

Notes

Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP18J14970.

Compliance with Ethical Standards

Conflict of interest

The author declare that they have no competing interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Takahiro Mizoguchi
    • 1
  • Masamitsu Shimazawa
    • 1
  • Kazuki Ohuchi
    • 1
  • Yoshiki Kuse
    • 1
  • Shinsuke Nakamura
    • 1
  • Hideaki Hara
    • 1
    Email author
  1. 1.Molecular Pharmacology, Department of Biofunctional EvaluationGifu Pharmaceutical UniversityGifuJapan

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