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Gene expression profile of aging human brain and its in vitro model

Research Project

Project/Area Number 13470135
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionIwate Medical University

Principal Investigator

TOHGI Hideo  Iwate Medical University, Neurology, Professor, 医学部, 教授 (90155490)

Co-Investigator(Kenkyū-buntansha) YAMAGATA Munehisa  Iwate Medical University, Neurology, Instructor, 医学部, 助手 (00295974)
NAGANE Yuriko  Iwate Medical University, Neurology, Instructor, 医学部, 助手 (10306003)
USTUGISAWA Kimiaki  Iwate Medical University, Neurology, Lecturer, 医学部, 講師 (00244913)
TAKAHASHI Satoshi  Iwate Medical University, Neurology, Lecturer, 医学部, 講師 (50216719)
ABE Takasi  Iwate Medical University, Neurology, Ass Professor, 医学部, 助教授 (30202667)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsaging / α7nAChR / cDNA array / cell cycle / extracellular-signal-regulated kinase / human brain / neurite outgrowth / PC12 / α7nAChR / ERK / DNAアレイ / 老化 / ニューロン / アセチルコリン受容体 / リン酸化
Research Abstract

Age-related changes in gene expression profile of postmortem human neocortex were investigated using cDNA array analysis. In the aging human neocortex, expression of mRNAs for neuron-specific cyclin dependent kinases (Cdks), nicotinic acetylcholine receptors (nAChRs) and molecules involved in promoting neurite outgrowth and/or neuronal plasticity decreased, and consequently increasing neuronal vulnerability might foster mRNAs expression counteractive against stresses.
PC12 cells transfected with the α7nAChR cDNA, independent of agonistic stimulation, exhibited to start the sustained expression of phospho-extracellular-signal-regulated kinases (ERKs) as immediately as expression of α7 subunit protein after transfection. PC12 cells over-expressing α7nAChR showed high migration ability, marked neurite outgrowth, adherence to the culture dish and an increase in expression of surface N-cadherin, whereas their proliferation activity was low. Examination of cell cycle distribution showed an increase in the proportion of G2-phase cells in PC 12 cells over-expressing α7nAChR. These findings suggest that, over-expression of α7nAChR induces sustained activation of ERK, which probably promotes the functions of neuron-specific Cdks and differentiation-like transformation. The cytoskeletal machinery necessary for sufficient expression of α7 nAChR may have some links to ERK and Cdk signals promoting neurite outgrowth, and their declines in the elderly may deteriorate neuronal plasticity.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgi H: "Over-expression of α7 nicotinic acetylcholine receptor prevents Gl-arrest and DNA fragmentation in PC12 cell hypoxia"J Neurochem. 81. 497-505 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgi H: "Over-expression of α7 nicotinic acetylcholine receptor induces sustained ERK phosphorylation and N-cadherin expression in PC12 cells"Mol Brain Res. 106. 88-93 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obara D, Utsugisawa K, Nagane Y, Tohgi H: "Hypoxic condition interferes with phosphorylation of Akt at Thr^<308> in cultured rat PC12 cells"Neurosci Lett. 332. 167-170 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohgi H, Takahashi S, Abe T, Utsugisawa K.: "Symptomatic characteristics of parkinsonism and the width of substantia nigra pars compacta on MRI according to ischemic changes in the putamen and cerebral white matter : Implication for the diagnosis of vascular parkinsonism"Eur.Neurol. 46. 1-10 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mihara M, Utsugisawa K, Konno S, Tohgi H: "Isolated lesions limited to the bilateral substantia nigra on MRI associated with influenza A infection"Eur Neurol. 45. 290-291 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagane Y, Utsugisawa K, Obara D, Tohgi H: "NKT-associated markers and perforin in hyperplastic thymuses from patients with myasthenia gravis"Muscle Nerve. 24. 1359-1364 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgj H: "Over-expression of α7 nicotinic acetylcholine receptor prevents G1-arrest and DNA fragmentation in PC12 cells after hypoxia"J Neurochem. 81. 497-505 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgj H: "Over-expression of α7 nicotinic acetylcholine receptor induces sustained ERK phosphorylation and N-cadherin expression in PC12 cells"Mol Brain Res. 106. 88-93 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obara D, Utsugisawa K, Nagane Y, Tohgj H: "Hypoxic condition interferes with phosphorylation of Akt at Thr^<308> in cultured rat PC12 cells"Neurosci Lett. 332. 167-170 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Munakata R, Utsugisawa K, Nagane Y, Yamagata M, Oikawa M, Obara D, Tohgi H: "The Effect of Combined Therapy with Iminunoadsorption and High-Dose Intravenous Methylprednisolone on Myasthenia Gravis"Eur Neurol. 48. 115-117 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tohgi H, Takahashi S, Abe T, Utsugisawa K: "Symptomatic characteristics of parkinsonism and the width of substantia nigra pars compacta on MRI according to ischemic changes in the putamen and cerebral white matter : Implication for the diagnosis of vascular parkinsonism"Eur Neurol. 46. 1-10 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mihara M, Utsugisawa K, Konno S, Tohgi H: "Isolated lesions limited to the bilateral substantia nigra on MRI associated with influenza A infection"Eur Neurol. 45. 290-291 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagane Y, Utsugisawa K, Obara D, Tohgi H: "NKT-associated markers and perforin in hyperplastic thymuses from patients with myasthenia gravis"Muscle Nerve. 24. 1359-1364 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Kondoh R, Yonezawa H, Tohgi H: "Interleukin-2 production by peripheral blood mononuclear cells from patients with myasthenia gravis"Eur Neurol. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Yonezawa H, Obara D, Kondoh R, Tohgi H: "Effects of FK506 on myasthenia gravis patients with high interleukin-2 productivity in peripheral blood mononuclear cells"Muscle Nerve. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagane Y, Utsugisawa K, Obara D, Yamagata M, Tohgi H: "Dendritic cells in hyperplastic thymuses from patients with myasthenia gravis"Muscle Nerve. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgi H: "Over-expression of α7 nicotinic acetylcholine receptor prevents G1-arrest and DNA fragmentation in PC12 cells after hypoxia"J Neurochem. 81. 497-505 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Munakata R, Utsugisawa K, Nagane Y, Yamagata M, Oikawa M, Obara D, Tohgi H: "The Effect of Combined Therapy with Immunoadsorption and High-Dose Intravenous Methylprednisolone on Myasthenia Gravis"Eur Neurol. 48. 115-117 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Tohgi H: "Over-expression of α7 nicotinic acetylcholine receptor induces sustained ERK phosphorylation and N-cadherin expression in PC12 cells"Mol Brain Res. 106. 88-93 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obara D, Utsugisawa K, Nagane Y, Tohgi H: "Hypoxic condition interferes with phosphorylation of Akt at Thr^<308> in cultured rat PC12 cells"Neurosci Lett. 332. 167-170 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsugisawa K, Nagane Y, Yonezawa H, Obara D, Kondoh R, Tohgi H: "Effects of FK506 on myasthenia gravis patients with high interleukin-2 productivity in peripheral blood mononuclear cells"Muscle Nerve. (in press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Utsugisawa K, Nagane Y, Obara D, Kondoh R, Yonezawa H, Tohgi H: "Interleukin-2 production by peripheral blood mononuclear cells from patients with myasthenia gravis"Eur Neurol. (in press). (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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