Article

Journal of Molecular Neuroscience

, Volume 48, Issue 3, pp 508-517

First online:

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

  • Daisuke TsuchikawaAffiliated withDepartment of Anatomy, Showa University School of MedicineDepartment of Orthopedic Surgery, Showa University Fujigaoka Hospital
  • , Tomoya NakamachiAffiliated withDepartment of Anatomy, Showa University School of MedicineCenter for Biotechnology, Showa University
  • , Masashi TsuchidaAffiliated withDepartment of Anatomy, Showa University School of MedicineDepartment of Orthopedic Surgery, Showa University Fujigaoka Hospital
  • , Yoshihiro WadaAffiliated withDepartment of Anatomy, Showa University School of Medicine
  • , Motohide HoriAffiliated withDepartment of Anatomy, Showa University School of Medicine
  • , Jozsef FarkasAffiliated withDepartment of Anatomy, Showa University School of MedicineDepartment of Anatomy, University of Pecs
  • , Akira YoshikawaAffiliated withDepartment of Anatomy, Showa University School of Medicine
  • , Nobuyuki KagamiAffiliated withDepartment of Anatomy, Showa University School of Medicine
  • , Nori ImaiAffiliated withDepartment of Anatomy, Showa University School of Medicine
    • , Norihito ShintaniAffiliated withLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
    • , Hitoshi HashimotoAffiliated withLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka UniversityCenter for Child Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine
    • , Takashi AtsumiAffiliated withDepartment of Orthopedic Surgery, Showa University Fujigaoka Hospital
    • , Seiji ShiodaAffiliated withDepartment of Anatomy, Showa University School of Medicine Email author 

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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

PACAP Spinal cord injury Neuroprotective effect Knockout mouse