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Signal transdaction and gene expression in the pors associated with the overactive bladder following cerebra-vascular disease

Research Project

Project/Area Number 12470331
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKanazawa University

Principal Investigator

YOKOYAMA Osamu  Kanazawa Univ, Dept of Urdogg, Assistant Prof, 医学部・附属病院, 講師 (90242552)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Yasuo  Kanazawa Univ, Dept of Urol, Lecturer, 医学部・附属病院, 講師 (20322117)
KOMATSU Kazuto  Kanazawa Univ, Dept of Urol, Lecturer, 医学部・附属病院, 助手 (80291368)
NAMIKI Mikio  Kanazawa Univ, Dept of Urol, Prof, 大学院・医学系研究科, 教授 (70155985)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥11,400,000 (Direct Cost: ¥11,400,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥8,400,000 (Direct Cost: ¥8,400,000)
Keywordscorebro-vasuular disease / neurogenic bladder / bladder overactivity / urinary incontinence / protein kinase A / actinomycin 0 / neural plasticity / cox-2 / 脳梗塞 / 遺伝子 / アクモノマイシンD / 一酸化窒素合成酵素
Research Abstract

Object: To investigate the signal transduction and molecular mechanisms in the pontine tegmental area (PTA) associated with bladder overactivity after cerebral infarction. Methods: Cerebral infarction was induced by left middle cerebral artery occlusion (MCAO) in SD rats. Bladder activity was monitored with continuous infusion cystometrography in awake rats. The influences of H-89 (protein kinase A inhibitor), actinomycin D (ACD; RNA synthesis inhibitor), or NS-398 (COX-2 inhibitor) on bladder activity and gene expression (c-fos and zif268) were examined. Expressions of c-fos and zif268 mRNA in the DPT were monitored with real-time PCR. Results: In cerebral infarcted (CI) rats pretreated with vehicle, bladder capacity (BC) was significantly reduced after MCAO and remained consistently below half of pre-occlusion capacity. H-89, when administered 2 hours after MCAO, inhibited the reduction in BC. ACD also blocked reduction in BC in CI rats. In ACD-treated CI rats, BC gradually recovered … More and returned to the control level prior to MCAO within 10 hours. Treatment with NS-398 before MCAO prevented the development of bladder overactivity dose-dependently, and did not influence infarction volume. One hour after MCAO, c-fos and COX-2 mRNA expression, three hours after MCAO, zif268 mRNA expression had significantly increased as compared to those in sham operated rats. Pretreatment with MK-801, glutamatergic NMDA receptor antagonist, inhibited the development bladder overactivity and significantly reduced these gene expressions in the PTA. ACD suppressed an increase in c-fos mRNA expression 1hour after MCA occlusion as well as in zif268 3hours after MCAO. Conclusion: These results indicate that the development of bladder overactivity following MCAO is mediated by the activation of an NMDA receptor and by an RNA synthesis. Transcription in the DPT was found to be necessary for maintenance of long-lasting bladder overactivity caused by cerebral infarction. Furthermore, COX-2 molecular mechanism in the brain seems to be related to bladder overactivity. Further research on the molecular mechanisms in the brain related to bladder overactivity may lead to pharmacological therapy which targets the micturition center. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yaokoyama O, Yoshiyama M, et al.: "Changes in dopaminergic and glutamitergic excitatory mechanisms of micutyrition reflex after middle cerebral artery occasion in conscious rats"Exp. Neurol. 173. 129-135 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama K, Yokoyama O et al.: "Contribution of cerebral nitric oxide to bladder overactibity following cerebral interaction in rats"J. Urol. 167. 391-396 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Ootuka N, et al.: "Forebrain muscarinic control of micturition reflex in rats"Neuropharmacology. 41. 629-638 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yotsuyanagi S, Yokoyama O, et al.: "Expression of neural plasticity-related genes in pontine segmental area in rats with overactive bladder following cerebral infarction"J. Urol. 166. 1148-1155 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, et al.: "Interaction between dopaminergic and glutamatergic excitatory influences on lower winery tract function in normal and cerebral infracted rats"Exp Neurol. 169. 148-155 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, et al.: "Role of the forebrain in bladder over activity following cerebral infarction in the rat"Exp. Neurol. 163. 469-476 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 児玉浩一, 横山修: "脳梗塞ラットモデルを用いた研究法 神経泌尿器科学研究法"日本医学館. 172 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, Namiki M, de Groat WC: "Changes in dopaminergic and glutamatergic excitatory mechanisms of micturition reflex after middle cerebral artery occlusion in conscious rats"Exp Neurol. 173. 129-135 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kodama K, Yokoyama O, Komatsu K, Namiki M: "Contribution of cerebral nitric oxide to bladder overactivity following cerebral infarction in rats"J Urol. 167. 391-396 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Ootsuka N, Komatsu K, Kodama K, Yotsuyanagi S, Niikura S, Nagasaka Y, Nakada Y, Kanie S, Namiki M: "Forebrain muscarinic control of micturition reflex in rats"Neuropharmocology. 41. 629-638 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yotsuyanagi S, Yokoyama O, Komatsu K, Kodama K, Niikura S, Namiki M: "Expression of neural plasticity-related genes in pontine tegmental area in rats with overactive bladder following cerebral infarction"J Urol. 166. 1148-1155 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, Namiki M, de Groat WC: "Interaction between dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral infarcted rats"Exp Neurol. 169. 148-155 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishiura Y, Yoshityama M, Yokoyama. O, Namiki M, de Groat WC: "Central muscarinic mechanisms regulating voiding in rats"J Pharmacol Exp Therapeu. 297. 933-939 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakada M, Yokoyama O, Komatsu K, Kodama K, Yotsuyanagi S, Niikura S, Nagasaka Y, Namiki M: "Effects of aniracetam on bladder oyeractivity in rats with cerebral infarction"J Pharmacol Exp Therapeu. 293. 921-926 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, Namiki M, deGroat W: "Role of the forebrain in bladder overactivity following cerebral infarction in the rat"Exp Neurol. 163. 469-476 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Komatsu K, Kodama K, Yotsuyanagi S, Niikura S, Namiki M: "Diagnostic value of intravesical lidocaine for overactive bladder"J Urol. 164. 340-343 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanie S, Yokoyama O, Komatsu K, Kodama K, Yotsuyanagi S, Niikura S, Nagasaka Y, Miyamoto K, Namiki M: "GABAergic contribution to rat bladder hyperactivity following middle cerebral artery occlusion"Am J Physiol. 279. R1230-R1238 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, Namiki M, de Groat WC: "Changes in dopaminergic and glutamatergic excitatory mechanisms of micturition reflex after middle cerebral artery occlusion in conscious rats"Exp Neurol. 173. 129-135 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kodama K, Yokoyama O, Komatsu K, Namiki M: "Contribution of cerebral nitric oxide to bladder overactivity following cerebral infarction in rats"J Urol. 167. 391-396 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokoyama O, Ootsuka N, Komatsu K, Kodama K, Yotsuyanagi S, Niikura S, Nagasaka Y, Nakada Y, Kanie S, Namiki M: "Forebrain muscarinic control of micturition reflex in rats"Neuropharmocology. 41. 629-638 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yotsuyanagi S, Yokoyama O, Komatsu K, Kodama K, Niikura S, Namiki M: "Expression of neural plasticity-related genes in pontine tegmental area in rats with overactive bladder following cerebral infarction"J Urol. 166. 1148-1155 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokoyama O, Yoshiyama M, Namiki M, de Groat WC: "Interacttion between dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral infarcted rats"Exp Neurol. 169. 148-155 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakada M: "Effects of aniracetam on bladder overactivity in rats with cerebral infarction"J.Pharmacol.Exp.Ther. 293. 921-926 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yokoyama O: "Role of the forebrain in bladder overactivity following cerebral infarction in the rat"Exp Neurol. 163. 469-476 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yokoyama O: "Diagnostic value of intravesical lidocaine for overactive bladder"J.Urol. 164. 340-343 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kanie S: "GABA ergic contribution to rat bladder hyperactivity following middle cerebral artery occlusion"Am J Physiol. 279. R1230-R1238 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Komatsu K: "Central muscarinic mechanism of bladder overactivity associated with Alzheimer type senile dementia in a conscions rat model"Neurourol Urodyn. 19. 539-540 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yokoyama O: "Interaction between dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral infacted rats."Exp Neurol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 児玉浩一,横山修: "神経泌尿器科学研究法・脳梗塞ラットモデルを用いた研究法"日本医学館. 9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 四柳智嗣,横山修: "排尿障害"Medicament News. (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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