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

与阿尔茨海默型老年痴呆相关的膀胱过度活动的中枢毒蕈碱机制。

• 批准号: 10470334
• 负责人: YOKOYAMA Osamu
• 金额: $ 7.74万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470334/
• 关键词: Alzheimer dementia; neurogenic bladder; bladder overactivity; muscarine; brain; bladder; urinary incontinence; ibotenic acid; 膀胱

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

注意：为探讨Alzheimer型老年期痴呆（AD）神经源性膀胱过度活动的机制，采用清醒大鼠模型，将雄性Wistar大鼠置于立体定向仪中，用鹅膏蕈氨酸（IA）（每侧7.5 μg/只）损毁双侧基底前脑（BF大鼠）。将磷酸盐缓冲盐水（PBS）注射至对照大鼠（假手术大鼠; SO大鼠）。在IA/PBS注射后7至10天获得膀胱测压图（CMG）。在记录CMG后，检测额叶皮质胆碱乙酰转移酶（CAT）活性，以评估基底前脑至额叶皮质的胆碱能神经元投射的损伤。在清醒的BF或SO大鼠侧脑室注射毒蕈碱受体激动剂Oxotremorine M或M1受体拮抗剂哌仑西平，观察其对脑缺血的影响。还在BF大鼠中检查了哌仑西平的拮抗作用。氧化震颤素M或 ...更多信息 结果：在尿烷麻醉下，将哌仑西平直接注入PMC（脑桥排尿中心），膀胱容量明显减小。IA注射后7至10天，膀胱容量约为SO大鼠的43%。BF大鼠额叶皮质CAT活性降低。氧震颤素M增加BF大鼠膀胱容量，而减少SO大鼠膀胱容量。哌仑西平能显著增加BF和SO大鼠的膀胱容量，并能拮抗氧化震颤素M的作用。PMC内直接注射氧化震颤素M可降低BF和SO大鼠的膀胱容量，而注射哌仑西平对CMG无影响。结论：大脑皮层M1毒蕈碱系统对排尿反射通路有抑制作用。这种抑制机制的下调在阿尔茨海默型痴呆的膀胱过度活动症中起着重要作用。脑干M2毒蕈碱系统可能对排尿反射通路有兴奋性影响。少

项目成果

Ishiura Y, Yokoyama O, et al.: "Central muscarinic mechanisms regulating voiding in rats"Neurourol Urodyn. 18. 351-352 (1999)

Ishiura Y、Yokoyama O 等人：“调节大鼠排尿的中枢毒蕈碱机制”Neurourol Urodyn。

Ishimura Y, Yokoyama O, et al.: "Central muscarinic mechanisms regulating voiding in rats"Neurourol Urodyn. 18. 351-352 (1999)

Ishimura Y、Yokoyama O 等人：“调节大鼠排尿的中枢毒蕈碱机制”Neurourol Urodyn。

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)

Yokoyama, O, Kamatsu K 等人：“脑梗塞大鼠膀胱收缩力的变化与膀胱过度活动相关”J.

Nakada Y, Yokoyama O, et al.: "Effects of aniracetam on bladder overactivity in rats with cerebral infarction"J. Pharmacol. Exp Ther. (in press). (2000)

Nakada Y，Yokoyama O，等：“茴拉西坦对脑梗塞大鼠膀胱过度活动的影响”J。

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)

Naoki Otsuka、Kazuto Komatsu、Osamu Yokoyama 等人：“阿尔茨海默氏痴呆症的泌尿功能障碍：鹅膏蕈酸化学破坏基底前脑神经节引起的膀胱功能变化”日本泌尿外科协会杂志 90. 238 (1999)。