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

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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.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (TN, SS) and by a High-Technology Research Center Project (SS) from the Ministry of Education, Science, Sports and Culture of Japan, and Research on Health Sciences focusing on Drug Innovation from The Japan Health Sciences Foundation (SS) and Support Program for the Strategic Research Foundation at Showa University, 2008-2012.

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Authors and Affiliations

  1. Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan

    Daisuke Tsuchikawa, Tomoya Nakamachi, Masashi Tsuchida, Yoshihiro Wada, Motohide Hori, Jozsef Farkas, Akira Yoshikawa, Nobuyuki Kagami, Nori Imai & Seiji Shioda

  2. Department of Orthopedic Surgery, Showa University Fujigaoka Hospital, Kanagawa, Japan

    Daisuke Tsuchikawa, Masashi Tsuchida & Takashi Atsumi

  3. Center for Biotechnology, Showa University, Shinagawa-Ku, Tokyo, 142-8555, Japan

    Tomoya Nakamachi

  4. Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan

    Norihito Shintani & Hitoshi Hashimoto

  5. Center for Child Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Suita, Osaka, 565-0871, Japan

    Hitoshi Hashimoto

  6. Department of Anatomy, University of Pecs, Pecs, Hungary

    Jozsef Farkas

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  1. Daisuke Tsuchikawa
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  2. Tomoya Nakamachi
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  3. Masashi Tsuchida
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  4. Yoshihiro Wada
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  5. Motohide Hori
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  6. Jozsef Farkas
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  7. Akira Yoshikawa
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  8. Nobuyuki Kagami
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  9. Nori Imai
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  10. Norihito Shintani
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  11. Hitoshi Hashimoto
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  12. Takashi Atsumi
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  13. Seiji Shioda
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Correspondence to Seiji Shioda.

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Tsuchikawa, D., Nakamachi, T., Tsuchida, M. et al. Neuroprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Spinal Cord Injury. J Mol Neurosci 48, 508–517 (2012). https://doi.org/10.1007/s12031-012-9817-2

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  • DOI: https://doi.org/10.1007/s12031-012-9817-2

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