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2000 Fiscal Year Final Research Report Summary

Inhibition of neuronal cell death in Parkinson's disease by transduction of neurotrophic factor gene.

Research Project

Project/Area Number 11670640
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionJUNTENDO UNIVERSITY

Principal Investigator

MORI Hideo  Juntendo University, Neurology, Associate professor, 医学部, 助教授 (30150634)

Co-Investigator(Kenkyū-buntansha) MIZUNI Yoshikuni  Juntendo University, Neurology, Professor, 医学部, 教授 (30049043)
MOCHIZUKI Hideki  Juntendo University, Neurology, Assistant professor, 医学部, 講師 (90230044)
Project Period (FY) 1999 – 2000
KeywordsPigment epitheliurm-derived factori / Neurotrophic factor / Substantia nigra / Striatum / Apoptosis / Adeno-associated virus / Gene therapy
Research Abstract

Pigment epithelium-derived factor (PEDF), a neurotrophic agents first identified in conditioned medium from cultured human retinal pigment epithelial cells, induces neuronal differentiation with neuritic outgrowth in Y-79 retinoblastoma cells and has a neurotrophic survival effect on cerebellar granule cells in culture. PEDF also have protective effect against glutamate toxicity and induction of apoptotic cell death of cultured granular cells. In this project, first we investigated the effects of human recombinant PEDF (hrPEDF) on proliferation of cultured nigral neurones. To do this experiments, we used cultures of nigral neurones isolated from the fetal rat brains. The number of nigral neurones, which identified by immunohistochemistry for tyrosine hydroxilase, is larger in the presence of PEDF than that of controls. The effect of PEDF showed a dose-response relationship. In second studies, we have performed the transduction of PEDF gene to the striatum and nigra of mice. To this purpose, we used recombinent adeno-associated (AAV) vectors which are sufficient for packaging and integration. AAV containing cDNA encoding PEDF and GFP were injected to the striatum of the mice by streotaxic operation. GFP-positive cells were observed in the striatum and the substantia nigra, which were transported through strionigral pathway. We are now conducting immunohistochemistry for PEDF on these sections to confirm the expression of the PEDF.Our study suggest the possibility of PEDF gene transfer to the striatum and nigra and effect of survival of niral neurones, and furthermore potential role for the gene therapy of Parkinson's disease

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Takanashi M,Mochizuki H,Yokomizo K,Hattori N,Mori H,et al.: "Iron accumulation in the substantia nigra of autosomal recessive javenile parkinsonism"Parkinson's disease and related disorders. in press.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka R, Kobayashi T,Motoi Y,Anno M,Mizuno Y,Mori H: "A case of foontotemporal dementia with tau P301L mutation in the Far East"J Neurol. 247. 705-707 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okuma Y,Urabe T,Mochizuki H,Miwa H,Shimo Y,Mori H,Mizuno Y: "A symmetric cortico-Cortical inhibitions in patients with Progressiue limb-kine Gc apraxia"Acta Neurol Scand. 102. 244-248 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mizuno Y,Hattori N,Mori H: "Genetics of Parkinson's desease"Biomed Phormacother. 59. 109-116 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugita Y,Zhao B,Shananler P,Dantirs F,et al.: "CNS interleulin-3(IL-3)expression and neurologiul syndrone in antisense-IL-3 transgenic mice"J Neuropathol Exp Neurol. 58. 480-488 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takanashi M, Mochizuki H, Yokomizo K Hattroi N, Mori H, Yamamura Y, Mizuno Y: "Iron accumulation in the substantia nigra of autosomal recessive juvenile parkinsonism (ARJP)"Parkinson disease and related disorders. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cohen J, Sugita Y, Chader GJ, Schwartz JP: "Recombinant forms of the neurotrophic factor pigment epithelium-derived factor activate cellular metabolism and inhibit proliferation of the RAW macrophage cell line."Neuroimmunomodulation. 7(1). 51-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tanaka R, Kobayashi T, Motoi Y, Anno M, Mizuno Y, Mori H: "A case of frontotemporal dementia with tau P301L mutation in the Far East"J Neurol. 247. 705-7 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okuma Y, Urabe T, Mochizuki H, Miwa H, Shimo Y, Mori H, Mizuno Y: "Asymmetric cortico-cortical inhibition in patients with progressive limb-kinetic apraxia"Acta Neurol Scand. 102(4). 244-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] MIzuno Y, Hattori N, Mori H: "Genetics of Parkinson's disease."Biomed Pharmacother. 53. 109-116 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugita Y, Zhao B, Shankar P, Dunbar CE, Doren S, Young HA, Schwartz JP: "CNS interleukin-3 (IL-3) expression and neurological syndrome in antisense-IL-3 transgenic mice."J Neuropathol Exp Neurol. 58. 480-8 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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