title: PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neurotrophic activities including modulation of synaptic plasticity and memory, hippocampal neurogenesis, and neuroprotection, most of which are shared with brain-derived neurotrophic factor (BDNF). Therefore, the aim of this study was to compare morphological effects of PACAP and BDNF on primary cultured hippocampal neurons. At days in vitro (DIV) 3, PACAP increased neurite length and number to similar levels by BDNF, but vasoactive intestinal polypeptide showed much lower effects. In addition, PACAP increased axon, but not dendrite, length, and soma size at DIV 3 similarly to BDNF. The PACAP antagonist PACAP6-38 completely blocked the PACAP-induced increase in axon, but not dendrite, length. Interestingly, the BDNF-induced increase in axon length was also inhibited by PACAP6-38, suggesting a mechanism involving PACAP signaling. K252a, a TrkB receptor inhibitor, inhibited axon outgrowth induced by PACAP and BDNF without affecting dendrite length. These results indicate that in primary cultured hippocampal neurons, PACAP shows morphological actions via its cognate receptor PAC1, stimulating neurite length and number, and soma size to a comparable extent as BDNF, and that the increase in total neurite length is ascribed to axon outgrowth.
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Katsuya
authors: K
authors: Ogata
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Norihito
authors: N
authors: Shintani
authors: 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, Yamadaoka, Suita, Osaka, Japan.
authors: Atsuko
authors: A
authors: Hayata-Takano
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Toshihiko
authors: T
authors: Kamo
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Shintaro
authors: S
authors: Higashi
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan; Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Kaoru
authors: K
authors: Seiriki
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Hisae
authors: H
authors: Momosaki
authors: Neurotrophic Factor and Neuronal Differentiation Team, INSERM U982, DC2N, University of Rouen, Mont-Saint-Aignan, France; PRIMACEN, Cell Imaging Platform of Normandy, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors: David
authors: D
authors: Vaudry
authors: Neurotrophic Factor and Neuronal Differentiation Team, INSERM U982, DC2N, University of Rouen, Mont-Saint-Aignan, France; PRIMACEN, Cell Imaging Platform of Normandy, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors: Hubert
authors: H
authors: Vaudry
authors: PRIMACEN, Cell Imaging Platform of Normandy, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France.
authors: Ludovic
authors: L
authors: Galas
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan; Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Atsushi
authors: A
authors: Kasai
authors: iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Kazuki
authors: K
authors: Nagayasu
authors: iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Takanobu
authors: T
authors: Nakazawa
authors: 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, Yamadaoka, Suita, Osaka, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
authors: Ryota
authors: R
authors: Hashimoto
authors: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Yukio
authors: Y
authors: Ago
authors: 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, Yamadaoka, Suita, Osaka, Japan; Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Toshio
authors: T
authors: Matsuda
authors: Faculty of Pharmaceutical Sciences, Hyogo University of Health Science, Minatojima, Chuo-ku, Kobe, Hyogo, Japan.
authors: Akemichi
authors: A
authors: Baba
authors: Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, 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, Yamadaoka, Suita, Osaka, Japan; iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan.
authors: Hitoshi
authors: H
authors: Hashimoto
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C495402:Adcyap1 protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide; D020813:Receptor, trkB