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Central muscarinic mechanisms of bladder overactivity associated with Alzheimer type senile dementia.

Research Project

Project/Area Number 10470334
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  University Hospital, Kanazawa University Assistant Professor., 医学部・附属病院, 講師 (90242552)

Co-Investigator(Kenkyū-buntansha) KOMATU Kazuto  University Hospital, Kanazawa University Assistant Professor., 医学部・附属病院, 助手 (80291368)
KO Eitetu  University Hospital, Kanazawa University Assistant Professor., 医学部・附属病院, 助手 (90283134)
NAMIKI Mikio  School of Medicine, Kanazawa University Professor, 医学部, 教授 (70155985)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1999: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1998: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsAlzheimer dementia / neurogenic bladder / bladder overactivity / muscarine / brain / bladder / urinary incontinence / ibotenic acid / 膀胱
Research Abstract

OBJECTS : To investigate the mechanisms of neurogenic bladder overactivity in Alzheimer type senile dementia in a conscious rat model.
METHODS : Male Wistar rats were placed in a stereotaxic apparatus, and subjected to bilateral lesion of the basal forebrain by means of ibotenic acid (IA) injection (7.5 μg/rat on each side)(BF rats). Phosphate buffered saline (PBS) was injected to control rats (sham operated rats ; SO rats). Cystometrograms (CMG) were obtained 7 to 10 days after IA/PBS injection. After CMG recording, choline-acetyltransferase (CAT) activities in the frontal cortices were assayed to assess the damage to cholinergic neuronal projections from basal forebrain to frontal cortices. The influences of intracerebroventricular administration of Oxotremorine M, muscarinic receptor agonist, or pirenzepine, M1 muscarinic receptor antagonist were investigated in conscious BF or SO rats. Antagonized effects of pirenzepine were also examined in BF rats. The effects of oxotremorine M or … More pirensepine directly injected into the PMC (pontine micturition center) were examined under urethane anesthesia.
RESULTS : Bladder capacity become significantly smaller than before IA injection. Seven to 10 days after IA injection, bladder capacity was approximately 43% of SO rats. CAT activity in the frontal cortices was reduced in BF rats. Oxotremorine M increased bladder capacity in BF rats, while decreased in SO rats. Pirensepine significantly increased bladder capacity both in BF and SO rats, and antagonised the effect of oxotremorine M. Direct injection of oxotremorine M into the PMC decreased bladder capacity in BF and SO rats, while injection of pirensepine had no effects on CMG.
CONCLUSIONS : These results indicate that M1 muscarinic system in the cerebral cortex has inhibitory influence to micturition reflex pathway. Down-regulation of this inhibitory mechanism plays an important role on overactive bladder in Alzheimer type dementia. M2 muscarinic system in the brainstem is likely to have excitatory influence on micturition reflex pathway. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Yokoyama, O, Kamatsu K et al.: "Change in bladder contractility associated with bladder overactivity in rats with cerebral infarction"J. Urol. 159. 577-580 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Ishiura Y, et al.: "Effects of MK-801 on bladder overactivity in rats with cerebral infarction"J. Urol. 159. 571-576 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, et al.: "Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion"Am. J. Physiol. 276. R935-R942 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishimura Y, Yokoyama O, et al.: "Central muscarinic mechanisms regulating voiding in rats"Neurourol Urodyn. 18. 351-352 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura Y, Yokoyama O, et al.: "Effects of nifedipine on bladder overactivity in rats with cerebral infarction"J. Urol. 162. 1502-1507 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakada Y, Yokoyama O, et al.: "Effects of aniracetam on bladder overactivity in rats with cerebral infarction"J. Pharmacol. Exp Ther. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 横山 修: "尿失禁に対する経膣的手術のコツ.臨床泌尿器科のコツと落とし穴"中山書店. 165 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 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
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Komatsu K, et al: "Change in bladder contractility associated with bladder overactivity in rats with cerebral infarction"J. Urol. 159. 577-580 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Ishiura Y, et al: "Effects of MK-801 on bladder overactivity in rats with cerebral infarction"J. Urol. 159. 571-576 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M, et al: "Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery ocelasion"Am J. Physiol. 276. R935-R942 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ishiura Y, Yokoyama O, Namiki M, et al: "Central muscarinic mechanisms regulating voiding in rats"Neurourol Urodyn. 18. 351-352 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura Y, Yokoyama O, et al: "Effeits of nitedipine on bladder overactivity in rats with cerebral infarction."J Urol. 162. 1502-1507 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yokoyama O, Yoshiyama M., et al.: "Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after cerebral artery occlusion"Am J. Physiol. 276. R935-R942 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishiura Y, Yokoyama O, et al.: "Central muscarinic mechanisms regulating voiding in rats"Neurourol Urodyn. 18. 351-352 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakamura Y, Yokoyama O, et al.: "Effects of nifedipine on bladder overactivity in rats with cerebral infarction"J. Urol. 162. 1502-1509 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshiyama M, Nezu FM, Yokoyama O, et al.: "Influence of glutamate receptor antagonists on micturition in rats with spinal cord injury"Exp. Neurol. 159. 250-257 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshiyama M, Nezu FM, Yokoyama O, et al.: "Changes in micturition after spinal cord injury in rats"Urology. 54. 929-933 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jang SY, Fraser MO, Ozawa H, Yokoyama O, et al.: "Urethral afferent nerve activity effects the micturition reflex implication for the relationship between stress incontinence and detrusor instability"J Urol. 162. 204-212 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 横山 修: "尿失禁に関する経腔的手術のコツ、臨床泌尿器科のコツと落とし穴3手術療法"中山書店. 165 (1999)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [Publications] 横山 修: "実験モデルを用いた排尿障害の基礎的研究" 日本泌尿器科学会雑誌. 90. 73 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大塚直樹、小松和人、横山修他: "アルツハイマー型痴呆における排尿障害:イボテン酸の前脳基底核化学破壊によって引き起こされる膀胱機能の変化" 日本泌尿器科学会雑誌. 90. 238 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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