IL-6 and PACAP receptor expression and localization after global brain ischemia in mice.
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.
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Tomoya
T
Nakamachi
Masashi
M
Tsuchida
Nobuyuki
N
Kagami
Sachiko
S
Yofu
Yoshihiro
Y
Wada
Motohide
M
Hori
Daisuke
D
Tsuchikawa
Akira
A
Yoshikawa
Nori
N
Imai
Keisuke
K
Nakamura
Satoru
S
Arata
Seiji
S
Shioda
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002545:Brain Ischemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism; D016893:Carotid Stenosis / Q000150:complications; D004277:DNA, Single-Stranded / Q000032:analysis; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D017966:Pyramidal Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000096:biosynthesis* / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000096:biosynthesis / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors
C495504:Adcyap1r1 protein, mouse; C117632:Adnp protein, mouse; D004277:DNA, Single-Stranded; D018398:Homeodomain Proteins; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C577686:interleukin-6, mouse