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

Autor: Sachiko Yofu, Yoshihiro Wada, Keisuke Nakamura, Masashi Tsuchida, Akira Yoshikawa, Satoru Arata, Tomoya Nakamachi, Nori Imai, Nobuyuki Kagami, Daisuke Tsuchikawa, Seiji Shioda, Motohide Hori
Rok vydání: 2012
Předmět:
Zdroj: Journal of Molecular Neuroscience. 48:518-525
ISSN: 1559-1166
0895-8696
DOI: 10.1007/s12031-012-9819-0
Popis: 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.
Databáze: OpenAIRE