Journal of Molecular Neuroscience

, Volume 48, Issue 3, pp 508–517

Neuroprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Spinal Cord Injury

Authors

  • Daisuke Tsuchikawa
    • Department of AnatomyShowa University School of Medicine
    • Department of Orthopedic SurgeryShowa University Fujigaoka Hospital
  • Tomoya Nakamachi
    • Department of AnatomyShowa University School of Medicine
    • Center for BiotechnologyShowa University
  • Masashi Tsuchida
    • Department of AnatomyShowa University School of Medicine
    • Department of Orthopedic SurgeryShowa University Fujigaoka Hospital
  • Yoshihiro Wada
    • Department of AnatomyShowa University School of Medicine
  • Motohide Hori
    • Department of AnatomyShowa University School of Medicine
  • Jozsef Farkas
    • Department of AnatomyShowa University School of Medicine
    • Department of AnatomyUniversity of Pecs
  • Akira Yoshikawa
    • Department of AnatomyShowa University School of Medicine
  • Nobuyuki Kagami
    • Department of AnatomyShowa University School of Medicine
  • Nori Imai
    • Department of AnatomyShowa University School of Medicine
  • Norihito Shintani
    • Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical SciencesOsaka University
  • Hitoshi Hashimoto
    • Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical SciencesOsaka University
    • Center for Child Mental Development, United Graduate School of Child DevelopmentOsaka University, Kanazawa University and Hamamatsu University School of Medicine
  • Takashi Atsumi
    • Department of Orthopedic SurgeryShowa University Fujigaoka Hospital
    • Department of AnatomyShowa University School of Medicine
Article

DOI: 10.1007/s12031-012-9817-2

Cite this article as:
Tsuchikawa, D., Nakamachi, T., Tsuchida, M. et al. J Mol Neurosci (2012) 48: 508. doi:10.1007/s12031-012-9817-2

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide expressed in the central nervous system. To date, changes in the expression and effect of endogenous PACAP have not been clarified with respect to spinal cord injury (SCI). The aim of this study was to elucidate the expression pattern and function of endogenous PACAP on the contusion model of SCI using heterozygous PACAP knockout (PACAP+/−) and wild-type mice. Real-time polymerase chain reaction methods revealed that the level of PACAP mRNA increased gradually for 14 days after SCI and that PAC1R mRNA levels also increased for 7 days compared with intact control mice. PACAP and PAC1R immunoreactivities colabeled with a neuronal marker in the intact spinal cord. Seven days after SCI, PAC1R immunoreactivity was additionally co-expressed with an astrocyte marker. Wild-type mice gradually recovered motor function after 14 days, but PACAP+/− mice showed significantly impaired recovery from 3 days compared with wild-type mice. The injury volume at day 7 in PACAP+/− mice, and the number of single-stranded DNA-immunopositive cells as a marker of neuronal cell death at day 3 were significantly higher than values measured in wild-type mice. These data suggest that endogenous PACAP is upregulated by SCI and has a neuroprotective effect on the damaged spinal cord.

Keywords

PACAPSpinal cord injuryNeuroprotective effectKnockout mouse

Copyright information

© Springer Science+Business Media, LLC 2012