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IL-6 and PACAP Receptor Expression and Localization after Global Brain Ischemia in Mice

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts a neuroprotective action against ischemic damage. This action is mediated by the interleukin-6 (IL-6) pathway. However, as the expression patterns of PACAP receptors and IL-6 following ischemia are not understood, we evaluated them in the mouse hippocampus in response to ischemia induced by bilateral common carotid artery occlusion. Real-time PCR determination of PAC1R mRNA expression in the hippocampus was significantly elevated on day 7 after ischemia. VPAC1R mRNA expression was significantly decreased 3 days after the ischemic episode, while VPAC2R mRNA expression showed a nonsignificant tendency to increase on day 7. IL-6 mRNA expression was significantly increased on day 3 and peaked on day 7 after ischemia. The mRNA expression of activity-dependent neuroprotective protein, which is a neuroprotective factor stimulated by PACAP, remained virtually unchanged in response to ischemia. IL-6 immunoreactivity was detected in the CA1 pyramidal cell layer and colocalized with the neuronal marker NeuN on day 1 after ischemia. On day 3, irregularly shaped IL-6-immunopositive cells colocalized with the astrocytic marker glial fibrillary acidic protein but not with the microglial marker Iba1. PAC1R immunoreactivity co-labeled with IL-6 immunoreactivity. These results suggest that PACAP could stimulate IL-6 secretion by neurons during the acute phase after an ischemic episode and thereafter by astrocytes during the subacute phase.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (T.N. and S.S.) and the High-Technology Research Center Project (S.S.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and Research on Health Sciences focusing on Drug Innovation from the Japan Health Sciences Foundation (S.S) 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

    Tomoya Nakamachi, Masashi Tsuchida, Nobuyuki Kagami, Sachiko Yofu, Yoshihiro Wada, Motohide Hori, Daisuke Tsuchikawa, Akira Yoshikawa, Nori Imai, Keisuke Nakamura & Seiji Shioda

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

    Tomoya Nakamachi & Satoru Arata

  3. Department of Forensic Medicine and Molecular Pathology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Motohide Hori

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  1. Tomoya Nakamachi
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  2. Masashi Tsuchida
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  3. Nobuyuki Kagami
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  12. Seiji Shioda
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Correspondence to Seiji Shioda.

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Nakamachi, T., Tsuchida, M., Kagami, N. et al. IL-6 and PACAP Receptor Expression and Localization after Global Brain Ischemia in Mice. J Mol Neurosci 48, 518–525 (2012). https://doi.org/10.1007/s12031-012-9819-0

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  • DOI: https://doi.org/10.1007/s12031-012-9819-0

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