Clarification of new brain peptide's pathophysiologic role and molecular mechanism in arthritic animal model.

• Project/Area Number: 16591518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Occupational and Environmental Health
• Principal Investigator: OHNISHI Hideo UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 講師 (20279342)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Toshitaka UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50082235) ; UETA Yoichi UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (10232745) ; OKIMOTO Nobukazu UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (70330991)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: RHEUMATOID ARTHRITIS / NEUROPEPTIDE / HYPOTHALAMUS / GALANIN-LIKE PEPTIDE / GENE EXPRESSION / 2-BUTEN-4-OLIDE / VASOPRESSIN / OXYTOCIN / パゾプレッシン

Research Abstract

Galanin-like peptide (GALP) was found from searching for orphan receptor ligands. GALP is exists in the hypothalamic arcuate nucleus, however, there is no knowledge about its relationship between GALP and chronic arthritis. On the basis of these circumstances, the purpose of this study was to investigate influence of GALP for chronic stress particularly in experimental arthritis. Practically, we evaluated GALP gene expression not only in acute stress stimulation (osmotic challenge and LPS injection), but also in chronic inflammatory stress stimulation (adjuvant arthritis). In result, we clarified following facts. GALP gene expression at the arcuate nucleus neuron was dependent on leptin and regulated by blood sugar control caused by insulin administration. Osmotic challenge has a potent stimulation for influence in GALP gene expression at posterior pituitary cells. Increase of the GALP gene expression in chronic inflammatory stress was possibly regulated by prostaglandin system. Long before, various change of central nervous system based on chronic inflammatory stress in patients with rheumatoid arthritis has been reported in addition to typical joint deformity and inflammatory change. Almost various mechanisms in physiological reaction are still unknown. However, we have to evaluate furthermore about the influence of central nervous system especially hypothalamus in pathogenesis of rheumatoid arthritis which is peripheral chronic inflammatory disease.

Research Products

• [Journal Article] The short chain sugar acid, 2-buten-4-olide, activates oxytocin-secreting neurons but not arginine vasopressin-secreting neurons in the hypothalamus of rats (2006)
  • Author(s): Kawasaki M, Yamaga C, Onaka T, Saito J, Mera T, Hashimoto T, Fujaihara H, Okimoto N, Ohnishi H, Nakamura T, Ueta Y
  • Journal Title: Brain Research 1086(1) Pages: 133-141
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] THE SHORT CHAIN SUGAR ACID, 2-BUTEN-4-OLIDE, ACTIVATES OXYTOCIN-SECRETING NEURONS BUT NOT ARGININE VASOPRESSIN-SECRETING NEURONS IN THE HYPOTHALAMUS OF RATS (2006)
  • Author(s): KAWASAKI M, YAMAGA C, ONAKA T, SAITO J, MERA T, HASHIMOTO T, FUJAIHARA H, OKIMOTO N, OHNISHI H, NAKAMURA T, UETA Y.
  • Journal Title: BRAIN RESEARCH 1086(1) Pages: 133-141
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The short chain sugar acid,2-buten-4-olide, activates oxytocin-secreting neurons but not arginine vasopressin-secreting neurons in the hypothalamus of rats (2006)
  • Author(s): Kawasaki M, Ohnishi H, et al.
  • Journal Title: Brain Research (In press)
• [Journal Article] Induction of galanin-like peptide gene expression in the arcuate nucleus of the rat after acute but not chronic inflammatory stress. (2005)
  • Author(s): Saito, J., Ozaki, Y., Kawasaki, M., Ohnishi, H., Okimoto, N., Nakamura, T., Ueta, Y.
  • Journal Title: Molecular Brain Research 133(2) Pages: 233-241
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of immediate early genes and vasopressin heteronuclear RNA in the paraventricular and supraoptic nuclei of rats after acute osmotic stimulus (2005)
  • Author(s): Kawasaki M, Yamaguchi K, Saito J, Ozaki Y, Mera T, Hashimoto T, Fujaihara H, Okimoto N, Ohnishi H, Nakamura T, Ueta Y
  • Journal Title: Journal of Neuroendocrinology 17(4) Pages: 227-237
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] INDUCTION OF GALANIN-LIKE PEPTIDE GENE EXPRESSION IN THE ARCUATE NUCLEUS OF THE RAT AFTER ACUTE BUT NOT CHRONIC INFLAMMATORY STRESS. (2005)
  • Author(s): SAITO, J., OZAKI, Y., KAWASAKI, M., OHNISHI, H., OKIMOTO, N., NAKAMURA, T., UETA, Y.
  • Journal Title: MOLECULAR BRAIN RESEARCH 133(2) Pages: 233-241
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] EXPRESSION OF IMMEDIATE EARLY GENES AND VASOPRESSIN HETERONUCLEAR RNA IN THE PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF RATS AFTER ACUTE OSMOTIC STIMULUS (2005)
  • Author(s): KAWASAKI M, YAMAGUCHI K, SAITO J, OZAKI Y, MERA T, HASHIMOTO T, FUJAIHARA H, OKIMOTO N, OHNISHI H, NAKAMURA T, UETA Y.
  • Journal Title: JOURNAL OF NEUROENDOCRINOLOGY 17(4) Pages: 227-237
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of immediate early genes and vasopressin heteronuclear RNA in the paraventricular and supraoptic nuclei of rate after acute osmotic stimulus (2005)
  • Author(s): Kawasaki M, Ohnishi H, et al.
  • Journal Title: Journal of Neuroendocrinology 17(4) Pages: 227-237
• [Journal Article] Expression of immediate early genes and vasopressin heteronuclear RNA in the paraventricular and supraoptic nuclei of rats after acute osmotic stimulus. (2005)
  • Author(s): Kawasaki M, Okimoto N, Ohnishi H, Nakamura T, Ueta Y.
  • Journal Title: J Neuroendocrinol In press
• [Journal Article] Induction of galanin-like peptide gene expression in the arcuate nucleus of the rat (2005)
  • Author(s): Saito J, Ohnishi H, Okimoto N, Nakamura T, Ueta Y.
  • Journal Title: Brain Res Mol Brain Res. 18;133(2) Pages: 233-241
• [Journal Article] Galanin-like peptide gene expression in the hypothalamus and posterior pituitary of the obese fa/fa rat. (2004)
  • Author(s): Saito, J., Ozaki, Y., Kawasaki, M., Ohnishi, H., Okimoto, N., Nakamura, T., Ueta, Y.
  • Journal Title: Peptides 25(6) Pages: 967-974
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] GALANIN-LIKE PEPTIDE GENE EXPRESSION IN THE HYPOTHALAMUS AND POSTERIOR PITUITARY OF THE OBESE FA/FA RAT. (2004)
  • Author(s): SAITO, J., OZAKI, Y., KAWASAKI, M., OHNISHI, H., OKIMOTO, N., NAKAMURA, T., UETA, Y.
  • Journal Title: PEPTIDES 25(6) Pages: 967-974
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Galanin-like peptide gene expression in the hypothalamus and posterior pituitary of the obese fa/fa rat. (2004)
  • Author(s): Saito J, Ohnishi H, Okimoto N, Nakamura T, Ueta Y.
  • Journal Title: Peptides 25(6) Pages: 967-974