2000 Fiscal Year Final Research Report Summary
Muscarinic mechanism of Neurogenic Bladder overactivity in Alzheimer type senile dementia in a conscious rat model
| Project/Area Number |
11671541
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOMATSU Kazuto Assistant Professor, Kanazawa University School of medicine, 医学部・附属病院, 助手 (80291368)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Hiroshi Professor Hokuriku University, 薬学部, 教授 (40102743)
KOH Eitetsu Assistant Professor, Kanazawa University School of medicine, 医学部・附属病院, 助手 (90283134)
YOKOYAMA Osamu Associate Professor, Kanazawa University School of medicine, 医学部・附属病院, 講師 (90242552)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Alzheimer disease / Neurogenic Bladder / Overactive Bladder / Ach receptor / Oxotremorine M / pirenzepine |
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| 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(7.5mg/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 pirensepin
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e directly infected 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 in influence on micturition reflex pathway. Less
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