Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide that acts as a neurotransmitter, neuromodulator, and neurotrophic factor via three heptahelical G protein-coupled receptors: a PACAP-preferring (PAC 1) receptor and two vasoactive intestinal polypeptide (VIP)-shared (VPAC 1 and VPAC 2) receptors. However, this does not alter the authors’ adherence to PLOS ONE Editorial policies and criteria. Hubert Vaudry and Ryota Hashimoto are currently serving as editors for PLOS ONE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The co-author Drs. and D.V.) and grants for research from the Senri Life Science Foundation (N.S.) and the Uehara Memorial Foundation, Japan (N.S. and K.S.) the Japan-France Integrated Action Program (SAKURA) funded by JSPS and the Ministère des Affaires Etrangères in France (H.H. LS081 (H.H.) Research Fellowships for Young Scientists (K.O., S.H. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper.įunding: This work was supported in part by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research, KAKENHI, Grant Nos 10335367, 25670038 (N.S.), 25460100 (A.H.-T.), 25670037 (A.K.), 2629300122 (H.H.) the Funding Program for Next Generation World-Leading Researchers, Grant No. Received: JAccepted: JanuPublished: March 25, 2015Ĭopyright: © 2015 Ogata et al. PLoS ONE 10(3):Īcademic Editor: Michal Hetman, University of Louisville, UNITED STATES (2015) PACAP Enhances Axon Outgrowth in Cultured Hippocampal Neurons to a Comparable Extent as BDNF. These results indicate that in primary cultured hippocampal neurons, PACAP shows morphological actions via its cognate receptor PAC 1, 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.Ĭitation: Ogata K, Shintani N, Hayata-Takano A, Kamo T, Higashi S, Seiriki K, et al. K252a, a TrkB receptor inhibitor, inhibited axon outgrowth induced by PACAP and BDNF without affecting dendrite length. Interestingly, the BDNF-induced increase in axon length was also inhibited by PACAP6–38, suggesting a mechanism involving PACAP signaling. The PACAP antagonist PACAP6–38 completely blocked the PACAP-induced increase in axon, but not dendrite, length. In addition, PACAP increased axon, but not dendrite, length, and soma size at DIV 3 similarly to BDNF. 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. Therefore, the aim of this study was to compare morphological effects of PACAP and BDNF on primary cultured hippocampal neurons. 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).
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