Expression and distribution of pituitary adenylate cyclase-activating polypeptide receptor in reactive astrocytes induced by global brain ischemia in mice.

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neuroprotectant. We previously showed that PACAP receptor (PAC1R) immunoreactivity was elevated in reactive astrocytes after stab wound injury. However, the pattern of PAC1R expression in astrocytes after brain injury is still unknown. In this study, PAC1R expression was evaluated in mouse hippocampal astrocytes after bilateral common carotid artery occlusion. PAC1R mRNA levels in the hippocampus peaked on day 7, and glial fibrillary acidic protein (GFAP) mRNA levels increased from day 3 to day 7 after ischemia. We then observed co-localization of PAC1R and GFAP by double immunostaining. GFAP-immunopositive cells showed signs of hypertrophy 3 days after the ischemia, and by day 7 had fine processes, were hypertrophied, and are known as reactive astrocytes. A low number of PAC1R-immunopositive astrocytes were detectable in the hippocampal area until 3 days after ischemia. PAC1R-positive astrocytes were widely distributed in the hippocampus between day 7 and day 14 after ischemia, and they were converging around the damaged CA1 pyramidal cell layer by day 28. These results suggest that PAC1R might be expressed in the middle to late stage of reactive astrocytes and PACAP plays an important role in the reactive astrocytes after brain injury.

• Authors: Tomoya Nakamachi, Jozsef Farkas, Nobuyuki Kagami, Yoshihiro Wada, Motohide Hori, Daisuke Tsuchikawa, Masashi Tsuchida, Akira Yoshikawa, Nori Imai, Tomohiko Hosono, Satoru Atrata, Seiji Shioda
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 118 Pg. 55-9 ( 2013) ISSN: 0065-1419 [Print] Austria
• PMID: 23564104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• RNA, Messenger
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I

Topics

• Animals
• Astrocytes (metabolism)
• Brain Ischemia (pathology)
• Cell Count
• Disease Models, Animal
• Gene Expression Regulation (physiology)
• Glial Fibrillary Acidic Protein (genetics, metabolism)
• Hippocampus (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (metabolism)
• Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I (genetics, metabolism)
• Time Factors