2004 Fiscal Year Final Research Report Summary
Prevention of delayed neuronal cell death by PACAP and its molecular mechanism
| Project/Area Number |
14380354
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Showa University |
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Principal Investigator |
SHIODA Seiji Showa Univ., Sch.Med., Department of Anatomy, Professor., 医学部, 教授 (80102375)
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| 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)
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| Project Period (FY) |
2002 – 2004
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| Keywords | PACAP / IL-6 / Neuronal cell death / Hippocamnus / Rat / Mouse |
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| 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)
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[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
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Journal Title
Regul Pept 123
Pages: 61-67
Description
「研究成果報告書概要(欧文)」より
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[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
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Journal Title
J Comp Neurol 448
Pages: 203-216
Description
「研究成果報告書概要(欧文)」より
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