title: Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide originally isolated from ovine hypothalamus. Recently, we have shown that the PACAP receptor (PAC1-R) is expressed in reactive astrocytes following an in vivo stub wound brain injury. However, the functional role of PACAP has not yet been clarified. In order to investigate the effect of PACAP on the proliferation of reactive astrocytes, a scratch wound paradigm was applied to astrocytic monolayers. Following injury, there was an increase in PAC1-R and glial fibrillary acidic protein (GFAP) immunoreactivity in the astrocytes surrounding the scratch line. PACAP at concentrations of 10(-15) to 10(-7) M was applied immediately after scratching, and the proliferating astrocytes were visualized by multiple immunofluorescence labeling. The percentage of cells that colabeled for Ki67 (a marker of proliferating cells) and GFAP increased in the 10(-11)- and 10(-13)-M PACAP-treated groups. The proliferating astrocytes induced by PACAP treatment mainly occurred in the proximal wound area where many reactive astrocytes were observed. Pretreatment with the PACAP receptor antagonist PACAP6-38 significantly suppressed the PACAP-induced effects. These results strongly suggest that PACAP plays an important role in the proliferation of reactive astrocytes following nerve injury.
authors.affiliation: Department of Anatomy, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kanako
authors.initials: K
authors.lastname: Oshida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kagami
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Mori
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Satoru
authors.initials: S
authors.lastname: Arata
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yofu
authors.forename: Kimi
authors.initials: K
authors.lastname: Endo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Motohide
authors.initials: M
authors.lastname: Hori
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuchikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kato
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I