PMID- 25807538 OWN - NLM STAT- MEDLINE DCOM- 20160217 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 3 DP - 2015 TI - PACAP enhances axon outgrowth in cultured hippocampal neurons to a comparable extent as BDNF. PG - e0120526 LID - 10.1371/journal.pone.0120526 [doi] LID - e0120526 AB - 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. FAU - Ogata, Katsuya AU - Ogata K AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Shintani, Norihito AU - Shintani N AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Hayata-Takano, Atsuko AU - Hayata-Takano A AD - 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. FAU - Kamo, Toshihiko AU - Kamo T AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Higashi, Shintaro AU - Higashi S AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Seiriki, Kaoru AU - Seiriki K AD - 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. FAU - Momosaki, Hisae AU - Momosaki H AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Vaudry, David AU - Vaudry D AD - 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. FAU - Vaudry, Hubert AU - Vaudry H AD - 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. FAU - Galas, Ludovic AU - Galas L AD - PRIMACEN, Cell Imaging Platform of Normandy, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France. FAU - Kasai, Atsushi AU - Kasai A AD - 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. FAU - Nagayasu, Kazuki AU - Nagayasu K AD - iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Nakazawa, Takanobu AU - Nakazawa T AD - iPS Cell-based Research Project on Brain Neuropharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Hashimoto, Ryota AU - Hashimoto R AD - 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. FAU - Ago, Yukio AU - Ago Y AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka, Suita, Osaka, Japan. FAU - Matsuda, Toshio AU - Matsuda T AD - 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. FAU - Baba, Akemichi AU - Baba A AD - Faculty of Pharmaceutical Sciences, Hyogo University of Health Science, Minatojima, Chuo-ku, Kobe, Hyogo, Japan. FAU - Hashimoto, Hitoshi AU - Hashimoto H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adcyap1 protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I) RN - 0 (Receptors, Vasoactive Intestinal Peptide, Type II) RN - 37221-79-7 (Vasoactive Intestinal Peptide) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Axons/*metabolism/*physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cells, Cultured MH - Hippocampus/*metabolism/physiology MH - Mice MH - Mice, Inbred ICR MH - Neuronal Plasticity/physiology MH - Neurons/*metabolism/physiology MH - Pituitary Adenylate Cyclase-Activating Polypeptide/*metabolism MH - Receptor, trkB/metabolism MH - Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I/metabolism MH - Receptors, Vasoactive Intestinal Peptide, Type II/metabolism MH - Signal Transduction/physiology MH - Vasoactive Intestinal Peptide/metabolism PMC - PMC4373823 COIS- Competing Interests: The co-author Drs. Hubert Vaudry and Ryota Hashimoto are currently serving as editors for PLOS ONE. However, this does not alter the authors' adherence to PLOS ONE Editorial policies and criteria. EDAT- 2015/03/26 06:00 MHDA- 2016/02/18 06:00 PMCR- 2015/03/25 CRDT- 2015/03/26 06:00 PHST- 2014/07/19 00:00 [received] PHST- 2015/01/26 00:00 [accepted] PHST- 2015/03/26 06:00 [entrez] PHST- 2015/03/26 06:00 [pubmed] PHST- 2016/02/18 06:00 [medline] PHST- 2015/03/25 00:00 [pmc-release] AID - PONE-D-14-32345 [pii] AID - 10.1371/journal.pone.0120526 [doi] PST - epublish SO - PLoS One. 2015 Mar 25;10(3):e0120526. doi: 10.1371/journal.pone.0120526. eCollection 2015.