Biomedical subjects

Satoshi Yotsuyanagi

Publications and source records attributed to Satoshi Yotsuyanagi.

4 recordsLinked to original sources

PubMed2003

RNA synthesis in pons necessary for maintenance of bladder overactivity after cerebral infarction in rat.

PURPOSE: The maintenance of long lasting bladder overactivity caused by cerebral infarction is believed to require transcription in the pontine micturition center. Therefore, we examined the influence of the RNA synthesis inhibitor actinomycin D (Banyu Pharmaceutical Co., Ltd., Tokyo, Japan) on bladder overactivity induced by left middle cerebral artery occlusion. MATERIALS AND METHODS: Rats under halothane anesthesia were injected with actinomycin D or vehicle (mannitol) into the bilateral dorsal pontine tegmentum, followed by middle cerebral artery occlusion. Awake rats were cystometrically examined for 12 hours. The expression of c-fos and zif268 mRNA in the dorsal pontine tegmentum was monitored with real-time polymerase chain reaction. RESULTS: Injection of actinomycin D produced a significant decrease in bladder capacity in sham operated rats but bladder capacity returned to control levels before sham operation within 6 hours. In cerebral infarcted rats pretreated with vehicle bladder capacity was significantly decreased after middle cerebral artery occlusion and it remained consistently below half of pre-occlusion capacity. Actinomycin D blocked the decrease in bladder capacity in cerebral infarcted rats. In actinomycin D treated cerebral infarcted rats bladder capacity gradually recovered and returned to the control level before middle cerebral artery occlusion within 10 hours. Actinomycin D suppressed an increase in c-fos mRNA expression 1 hour after middle cerebral artery occlusion as well as in zif268 3 hours after occlusion. Administering actinomycin D 0.5 or 1 hour after middle cerebral artery occlusion also suppressed bladder overactivity until at least 10 hours after occlusion but injection 3 hours after occlusion did not. CONCLUSIONS: These results indicate that an RNA synthesis inhibitor can prevent a late stage of bladder overactivity. Transcription in the dorsal pontine tegmentum was found to be necessary to maintain the long lasting bladder overactivity caused by cerebral infarction.

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PubMed2002

Overactive bladder--experimental aspects.

Supra-pontine lesions resulting from neurological disorders such as vascular disease, Parkinson's disease, or Alzheimer type senile dementia lead to an increase in bladder activity. This is due in part to the removal at the cortical inhibitory control of the micturition center in the brain stem - i.e. the pontine micturition center (PMC) - and in part to facilitation of excitatory control. These inhibitory or excitatory controls consist of several neurotransmitter systems, including glutamate, dopamine, gamma-aminobutyric acid (GABA), and acetylcholine. Bladder overactivity caused by cerebral infarction is mediated by upregulation of N-methyl-D-aspartate (NMDA) glutamatergic and D2 dopaminergic excitatory mechanisms, and by downregulation of NMDA glutamatergic and Ml muscarinic inhibitory mechanisms in the brain. Bladder overactivity associated with Parkinson's disease is reportedly induced by a loss of input to the D1 dopaminergic receptor. Furthermore, bladder overactivity caused by Alzheimer type dementia is thought to be mediated by downregulation of M1 muscarinic inhibitory mechanisms. Development of bladder overactivity following cerebral infarction is mediated by activation of the NMDA receptor and accompanied by an increase in c-fos, zif268 and COX-2 mRNA expression in the dorsal pontine tegmentum.

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PubMed2002

Contribution of cerebral nitric oxide to bladder overactivity after cerebral infarction in rats.

PURPOSE: We investigated the contribution of cerebral nitric oxide to neurogenic voiding dysfunction after cerebral infarction. MATERIALS AND METHODS: The left mid cerebral artery in female Sprague-Dawley rats was occluded with 4-zero monofilament nylon thread. Bladder activity was monitored during infusion cystometrography. Time or dose dependent effects of intracerebral ventricular administration of the nonselective nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), were investigated in conscious, sham operated and cerebral infarcted rats. The selective neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl) imidazole was also administered to determine the participation of nitric oxide synthase subtypes. Cross-sectional infarct area was measured and infarct volume was calculated 12 hours after mid cerebral artery occlusion. RESULTS: Bladder capacity was reduced by 54% 30 minutes after mid cerebral artery occlusion. L-NAME significantly increased bladder capacity in a dose and time dependent manner in cerebral infarcted rats but had no effect on sham operated rats. L-NAME (50 microg./kg.) administered 3 or 5 hours after occlusion significantly increased bladder capacity. This effect of L-NAME was reversed by injecting 250 microg. L-arginine per rat, which alone did not produce any significant change in bladder capacity in cerebral infarcted rats. Administration of 1-(2-trifluoromethylphenyl) imidazole also significantly increased bladder capacity in these rats. On the other hand, 5 microg. of the nitric oxide donor FK-409 per rat reduced bladder capacity for 10 to 15 minutes. None of the drugs affected infarct volume. CONCLUSIONS: These results indicate that supraspinal nitric oxide has an important role in bladder overactivity after cerebral infarction but it does not affect normal micturition in rats. This finding suggests a central mechanism sensitive to nitric oxide for bladder overactivity after cerebral infarction.

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PubMed2002

A causative factor of copulatory disorder in rats following social stress.

PURPOSE: We investigated the causative role of testosterone in copulatory disorder and the expression of c-fos messenger (m)RNA in the medial preoptic area in rats after social stress. MATERIALS AND METHODS: To generate copulatory disorder rats in the experimental defeated group were attacked by residents for 10 minutes daily for 7 consecutive days (social stress). We then investigated the effect of repeat defeat on the frequency of mounting behavior and plasma testosterone levels. The effects of testosterone replacement and/or apomorphine (100 microg./kg. subcutaneously), a dopamine receptor agonist, on the frequency of mounting behavior were also studied. After experiencing social stress the brain area within the medial preoptic area was removed for analysis of c-fos and androgen receptor mRNA expression. Real-time reverse transcription-polymerase chain reaction was done to analyze gene expression. RESULTS: Rats in the defeated group showed a reduced frequency of mounting behavior and a decrease in plasma testosterone levels compared with values in control rats (p <0.01). After testosterone replacement the frequency of mounting behavior became significantly higher than that of socially stressed rat (p <0.05) but did not achieve control levels. The frequency of mounting behavior by socially stressed rats after apomorphine treatment was significantly higher than that of vehicle treated rats (p <0.05) but the frequency produced by the combination of testosterone replacement and apomorphine injection did not achieve control levels. After the social stress experience c-fos mRNA expression was significantly increased compared with that in control rats (p <0.05). The expression of androgen receptor mRNA was not affected by social stress. Testosterone replacement significantly reduced the expression of c-fos mRNA in the medial preoptic area (p <0.05). CONCLUSIONS: Our results indicate that a reduction in plasma testosterone may have a causative role in copulatory disorder induced by social stress. Changes in c-fos mRNA expression in the medial preoptic area correlated with copulatory disorder and, thus, they are suitable for monitoring that disorder.

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