2001 Fiscal Year Final Research Report Summary
Signal transdaction and gene expression in the pors associated with the overactive bladder following cerebra-vascular disease
| Project/Area Number |
12470331
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
YOKOYAMA Osamu Kanazawa Univ, Dept of Urdogg, Assistant Prof, 医学部・附属病院, 講師 (90242552)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Keywords | corebro-vasuular disease / neurogenic bladder / bladder overactivity / urinary incontinence / protein kinase A / actinomycin 0 / neural plasticity / cox-2 |
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| 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
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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
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