Neuroprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Spinal Cord Injury
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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.
KeywordsPACAP Spinal cord injury Neuroprotective effect Knockout mouse
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.
- Bracken MB (2012) Steroids for acute spinal cord injury. Cochrane Detabase Syst Rev 18:CD001046Google Scholar
- Kim WK, Kan Y, Ganea D, Hart RP, Gozes I, Jonakait GM (2000) Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway. J Neurosci 20:3622–3630PubMedGoogle Scholar
- Skoglosa Y, Lewen A, Takei N, Hillered L, Lindholm D (1999) Regulation of pituitary adenylate cyclase activating polypeptide and its receptor type 1 after traumatic brain injury: comparison with brain-derived neurotrophic factor and the induction of neuronal cell death. Neurosci 90:235–247CrossRefGoogle Scholar