title: Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Is Involved in Adult Mouse Hippocampal Neurogenesis After Stroke.
abstract: In the subgranular zone (SGZ) of the hippocampus, neurogenesis persists throughout life and is upregulated following ischemia. Accumulating evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to recovery after stroke. However, the mechanisms underlying the upregulation of neurogenesis are unclear. We have demonstrated that a neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exerts a wide range of effects on neural stem cells (NSCs) during neural development. Here, we examined the effects of endogenous and exogenous PACAP in adult NSCs of the SGZ. Immunostaining showed expression of the PACAP receptor PAC1R in nestin-positive NSCs of adult naive mice. PACAP injection into the lateral ventricle increased bromodeoxyuridine (BrdU)-positive proliferative cells in the SGZ. These data suggest that PACAP promoted the proliferation of NSCs. In global ischemia model mice, the number of BrdU-positive cells was increased in wild-type mice but not in PACAP heterozygous knockout mice. The BrdU-positive cells that increased in number after ischemia were immunopositive for SOX2, a marker of NSCs, and differentiated into NeuN-positive mature neurons at 4 weeks after ischemia. These findings suggest that PACAP contributes to the proliferation of NSCs and may be associated with recovery after brain injury.
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Toyama, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.affiliation: Center for Biotechnology, Showa University, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohtaki
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Murai
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.|Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Seki
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
authors.affiliation: Department of Neuropeptide Drug Discovery, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8051, Japan. Shioda@hoshi.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D064231:Nestin; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse
keywords: Global ischemia; Hippocampus; Neurogenesis; Pituitary adenylate cyclase-activating polypeptide