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2004 Fiscal Year Final Research Report Summary

Prevention of delayed neuronal cell death by PACAP and its molecular mechanism

Research Project

Project/Area Number 14380354
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Nerve anatomy/Neuropathology
Research InstitutionShowa University

Principal Investigator

SHIODA Seiji  Showa Univ., Sch.Med., Department of Anatomy, Professor., 医学部, 教授 (80102375)

Co-Investigator(Kenkyū-buntansha) FINAHASHI Hisayuki  Showa Univ., Sch. Med. Dept. of Anatomy, Assistant Professor, 医学部, 助教授 (20317514)
NAKJO Shigeo  Showa Univ., Sch.Pharm.Sd., Dept.of Biol.Chem., Assistant Professor, 薬学部, 助教授 (50119236)
YADA Toshihiko  Jichi Medical Sch., Sch.Med.Department of Physiology, Division of Integrative Physiology, Professor, 教授 (60166527)
SAWADA Makoto  Fujita Health Univ., Institute for Comprehensive Med.Sci., Professor, 総合医科学研究所, 教授 (10187297)
Project Period (FY) 2002 – 2004
KeywordsPACAP / IL-6 / Neuronal cell death / Hippocamnus / Rat / Mouse
Research Abstract

Ischemic delayed neuronal cell death (apoptotis) in the hippocampus is prevented by PACAP. PACAP inhibits the increasing activity of the MAP kinase family, especially on JNK/SAPK and p38, thereby protecting apoptotic cell death. After the ischemia-reperfusion, both pyramidal cells and astrocytes increased their expression of PACAP receptors (PAC1-Rs). The pyramidal cells degenerated but reactive astrocytes increased their expression of PAC 1-R. PACAP does not only inhibit apoptotic cell death directly, but also affects on astrocytes through PAC1-Rs. Interleukin-6 (IL-6), produced in astrocytes, has several effects on prevention of brain ischemia and trauma and stimulating neuronal growth. IL-6 secretion into the CSF was stimulated extremely after PACAP infusion, suggesting that PACAP stimulates IL-6 secretion from astrocytes. We studied the effects of PACAP on the wild type and IL-6 KO mice after brain ischemia. In wild-type animals, PACAP significantly inhibited cell death but in IL-6 KO animals no cytoprotective effect of PACAP was seen. These results suggest that PACAP inhibits apoptotic cell death partly through IL-6. It is considered that PACAP itself and IL-6, stimulated secretion by PACAP, both synergistically inhibit the JNK/SAPK and p38 signaling pathway, thereby protecting neuronal cell death. (1677 Words)

  • Research Products

    (44 results)

All 2005 2004 2003 2002

All Journal Article (43 results) Book (1 results)

  • [Journal Article] Magnesium sulfate therapy in patients with acute neuronal damage : The problem of intravenous administration.2005

    • Author(s)
      Dohi K.
    • Journal Title

      Crit.Care Med. 33

      Pages: 1-2

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide(PACAP) promotes differentiation of mouse neural stem sells into astrocytes.2005

    • Author(s)
      Ohno F.
    • Journal Title

      Regul.Pept 126

      Pages: 115-122

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Electron microscopy examination of galanin-like peptide (GALP)-containing neurons in the rat hypothalamus.2005

    • Author(s)
      Guan J.L.
    • Journal Title

      Regul.Pept 126

      Pages: 73-78

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Orexin/hypocretin excites serotonergic neurons in the dorsal raphe nucleus by synapse.2005

    • Author(s)
      Wang Q.P
    • Journal Title

      Regul.Pept 126

      Pages: 35-42

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Monoaminergic neuronal development is not affected in PACAP gene-deficient mice2005

    • Author(s)
      Ogawa T.
    • Journal Title

      Regul.Pept 126

      Pages: 103-108

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Morphological analysis of ghrelin and its receptor in the rat pancreas.2005

    • Author(s)
      Kageyama H.
    • Journal Title

      Regul.Pept 126

      Pages: 67-72

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunohistochemistry of cholecystokinin A receptor in the rat pancreas.2005

    • Author(s)
      Kageyama H
    • Journal Title

      Regul.Pept 126

      Pages: 137-144

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neuronal interactions between galanin-like peptide(GALP)- and orexin- or melanin-concentrating hormone(MCH)-containing neurons in the rat hypothalamus2005

    • Author(s)
      Takenoya F.
    • Journal Title

      Regul.Pept. 126

      Pages: 79-84

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Orexin-1 receptor expression after global ischemia in mice.2005

    • Author(s)
      Nakamachi T.
    • Journal Title

      Regul.Pept 126

      Pages: 49-54

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] State-dependent effects of orexin on the serotonergic dorsal raphe neurons in the rat.2005

    • Author(s)
      Takahashi K
    • Journal Title

      Regul.Pept 126

      Pages: 137-144

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of lipopolysaccharide on the transport of pituitary adenylate cyclase activating polypeptide across the blood-brain barrier.2005

    • Author(s)
      Nonaka N
    • Journal Title

      Exp.Neurol 191

      Pages: 137-144

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactivity in the brain of a teleost, Uranoscopus japonicus : immunohistocheinical relationship between PACAP and adenohypophysial hormones.2005

    • Author(s)
      Matsuda K, Nagano Y, Uchiyama M, Onoue S, Takahashi A, Kawauchi H, Shioda S
    • Journal Title

      Regul Pept 126

      Pages: 129-136

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of lipopolysaccharide on the transport of pituitary adenylate cyclase activating polypeptide across the blood-brain barrier.2005

    • Author(s)
      Nonaka N, Shioda S, Banks W A.
    • Journal Title

      Exp Neurol 191

      Pages: 137-144

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Monoaminergic neuronal development is not affected in PACAP KO mice.2005

    • Author(s)
      Ogawa T, Nakamachi T, Ohtaki H, Hashimoto H, N S, Baba A, Watanabe J, Kikuyama S, Shioda S
    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide promotes differentiation of mouse neural stem cells into astrocytes.2005

    • Author(s)
      Ohno F, Watanabe J, Sekihara H, Hirabayashi T, Arata S, Kikuyama S, Shioda S, Nakaya K, Nakajo S
    • Journal Title

      Regul Pept 126

      Pages: 115-122

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PACAPによる神経細胞死防御とその分子制御機構2004

    • Author(s)
      塩田清二
    • Journal Title

      日薬理誌 123・4

      Pages: 235-244

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 6^<th> VIP/PACAP 2003 Special Issue2004

    • Author(s)
      Shioda S
    • Journal Title

      Regul.Pept 123

      Pages: 1

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of tissue oxygen content by pituitary adenylate cyclase-activating polypeptide(PACAP)-treatment in the central nervous system of mice.2004

    • Author(s)
      Ohtaki H
    • Journal Title

      Regul.Pept 123

      Pages: 61-67

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of PAC1 receptor in rat thymus after irradiation.2004

    • Author(s)
      Tokuda N
    • Journal Title

      Regul.Pept 123

      Pages: 167-172

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of tumor necrosis factor α TNF after focal ischemia in mice2004

    • Author(s)
      Yin L.
    • Journal Title

      Neurosci.Lett. 370

      Pages: 30-35

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Expression of tumor necrosis factor α in nerve fibers andoligodendrocytes after transient focal ischemia in mice.2004

    • Author(s)
      Ohtaki H.
    • Journal Title

      Neurosci.Lett. 368

      Pages: 162-166

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ultrastructure of orexin-1 receptor immunoreactivities in the spinal cord dorsal horn.2004

    • Author(s)
      Guan J.L
    • Journal Title

      Peptides 25

      Pages: 1307-1311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mishandling of the therapeutic peptide glucagons generates cytotoxic amyloidogenic fibrils.2004

    • Author(s)
      Onoue S.
    • Journal Title

      Pharmaceut.Res. 21

      Pages: 1274-1283

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Immunohistochemical localization of eotaxin immunoreactivity in nasal polyps.2004

    • Author(s)
      Seto H.
    • Journal Title

      Acta Otolaryngol.Suppl. 553

      Pages: 99-104

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Airway remodeling : a comparison between fatal and no-fetal asthma.2004

    • Author(s)
      Chen F.H.
    • Journal Title

      J.Asthma 41

      Pages: 629-636

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effects of lipopolysaccaride on leptin transport across the blood-brain barrier.2004

    • Author(s)
      Nonaka N.
    • Journal Title

      Brain Res 1016

      Pages: 58-65

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical applications of real-time PCR for diagnosis and treatment of human cytomegalovirus infection in children.2004

    • Author(s)
      Chen F.H.
    • Journal Title

      Pediat.Alleg.Immunol. 15

      Pages: 210-215

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of IL-6 and tumor necrosis factor alpha in CYP 3A11 and 2C29 down-regulation by Bacillus calmette-guerin and Lipopolysaccharide in mouse liver.2004

    • Author(s)
      Ashino T.
    • Journal Title

      Drug Metab.Dispos. 32

      Pages: 707-714

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Choto-san(Kampo Medicine) for the Treatment of Headache.2004

    • Author(s)
      Dohi K.
    • Journal Title

      Headache 44

      Pages: 375

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Orexins(hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca signaling in reciprocal manner to leptin : orexigenic neuronal pathway in the mediobasal hypothalamus.2004

    • Author(s)
      Muroya S.
    • Journal Title

      Eur.J.Neurosci. 19

      Pages: 1524-1534

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pituitary Adenylate Cyclase Activating Polypeptide meditated intracrine signaling in the testis.2004

    • Author(s)
      Li M.
    • Journal Title

      Endocrine 23

      Pages: 59-76

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Neuronal protein kinase Cγ-dependent proliferation/hypertrophy of spinal cord astrocyte follwing repeated in vivo administration of morphine.2004

    • Author(s)
      Narita M.
    • Journal Title

      Eur.J.Neurosci. 19

      Pages: 479-484

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Pituitary adenylate cyclase activating polypeptide-mediated intracrine signaling in the testicular germ cells.2004

    • Author(s)
      Li M, Funahashi H, Mbikay M, Shioda S, Arimura A
    • Journal Title

      Endocrine 23

      Pages: 59-75

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effects of lipopolysaccharide on leptin transport across the blood-brain barrier.2004

    • Author(s)
      Nonaka N, Hileman S M, Shioda S, Vo T Q, Banks W A
    • Journal Title

      Brain Res 1016

      Pages: 58-65

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of pituitary adenylate cyclase-activating polypeptide 38(PACAP38) on tissue oxygen content--treatment in central nervous system of mice.2004

    • Author(s)
      Ohtaki H, Dohi K, Yofu S, Nakamachi T, Kudo Y, Endo S, Aruga T, Goto N, Watanabe J, Kikuyama S, Shioda S
    • Journal Title

      Regul Pept 123

      Pages: 61-67

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of PAC1 receptor in rat thymus after irradiation.2004

    • Author(s)
      Tokuda N, Hamasaki K, Mizutani N, Adachi Y, Sawada T, Funahashi H, Shioda S, Fukumoto T
    • Journal Title

      Regul Pept 123

      Pages: 167-172

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nucleoprotamine diet derived from salmon soft roe protects mouse hippocampal neurons from delayed cell death after transient forebrain ischemia.2003

    • Author(s)
      Matsunaga M, Ohtaki H, Takaki A, Iwai Y, Yin L, Mizuguchi H, Miyake T, Usumi K, Shioda S
    • Journal Title

      Neurosci Res 47

      Pages: 269-276

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A transgenic mouse mode for the detailed morphological study of astrocytes.2003

    • Author(s)
      Suzuki R, Watanabe J, Arata S, Funahashi H, Kikuyama S, Shioda S
    • Journal Title

      Neurosci Res 47

      Pages: 451-454

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of the receptor for pituitary adenylate cyclase-activating polypeptide (PAC1-R) in reactive astrocytes.2003

    • Author(s)
      Suzuki R, Arata S, Nakajo S, Ikenaka K, Kikuyama S, Shioda S
    • Journal Title

      Brain Res Mol Brain Res 115

      Pages: 10-20

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PACAP and its receptors exert pleiotropic effects in the nervous system by activating multiple signaling pathways.2002

    • Author(s)
      Zhou C J, Shioda S, Yada T, Inagaki N, Pleasure S J, Kikuyama S
    • Journal Title

      Curr Protein Pept Sci 3

      Pages: 423-439

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) prevents hippocampal neurons from apoptosis by inhibiting JNK/SAPK and p38 signal transduction pathways.2002

    • Author(s)
      Dohi K, Mizushima H, Nakajo S, Ohtaki H, Matsunaga S, Aruga T, Shioda S
    • Journal Title

      Regul Pept 109

      Pages: 83-88

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1.2002

    • Author(s)
      Mizushima H, Zhou C J, Dohi K, Horai R, Asano M, Iwakura Y, Hirabayashi T, Arata S, Nakajo S, Takaki A, Ohtaki H, Shioda S
    • Journal Title

      J Comp Neurol 448

      Pages: 203-216

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regional differences in PACAP transport across the blood-brain barrier in mice : a possible influence of strain, amyloid beta protein, and age.2002

    • Author(s)
      Nonaka N, Banks W A, Mizushima H, Shioda S, Morley J E
    • Journal Title

      Peptides 23

      Pages: 2197-2202

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] In Hypothermia for acute brain damage : pathomechanism and practical aspects(Hayashi N et al. Edit)2004

    • Author(s)
      Mihara Y
    • Total Pages
      94-97
    • Publisher
      Springer-Verlag Tokyo
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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