Expression of neural plasticity related gene in the pontine tegmental area of rats with overactive bladder after cerebral infarction.
OBJECTIVE
We investigated the expression of the neural plasticity related genes c-fos, zif268, c-jun, brain-derived neurotrophic factor and tissue plasminogen activator in the pontine tegmental area in rats with overactive bladder induced by cerebral infarction.


METHODS
Cerebral infarction was induced by left middle cerebral artery occlusion in female Sprague-Dawley rats. Bladder activity was monitored by continuous infusion cystometrography in awake rats. Specimens were obtained from the pontine tegmental area 1, 3, 5, 12 and 24 hours after cerebral infarction or sham operation. The effect of 0.1 mg./kg. intravenously of the N-methyl-d-aspartate glutamatergic receptor antagonist MK-801 on bladder activity, and c-fos and zif268 expression after middle cerebral artery occlusion were studied. Real-time reverse transcriptase-polymerase chain reaction was performed with the LightCycler system (Roche Diagnostics, Mannheim, Germany) to evaluate cerebral infarction influences on gene expression in the pontine tegmental area.


RESULTS
Bladder capacity in cerebral infarcted rats was significantly reduced 1 to 24 hours after middle cerebral artery occlusion compared with that of sham operated rats (p <0.05 to 0.01). One hour after occlusion mean c-fos messenger (m)RNA expression plus or minus standard error had significantly increased to 18.9 +/- 4.0 in terms of its density relative to the outer control in a sample obtained immediately after occlusion compared with that in sham operated rats (p <0.05). It returned to the control level within 3 hours after occlusion. Mean zif268 mRNA expression significantly increased to a relative density of 3.2 +/- 1.4 3 hours after middle cerebral artery occlusion (p <0.01) and returned to the control level within 5 hours after occlusion. The expressions of c-jun, brain-derived neurotrophic factor and tissue plasminogen activator was not influenced by occlusion. Pretreatment with MK-801 inhibited bladder overactivity and significantly reduced the expression of c-fos and zif268 mRNA in the pontine tegmental area.


CONCLUSIONS
These results indicate that the development of bladder overactivity after middle cerebral artery occlusion is mediated by activation of an N-methyl-d-aspartate receptor and accompanied by an increase in c-fos and zif268 mRNA expression in the pontine tegmental area.
Yotsuyanagi
S
S
Department of Urology, Kanazawa University School of Medicine, Kanazawa, Japan.
Yokoyama
O
O
Komatsu
K
K
Kodama
K
K
Niikura
S
S
Namiki
M
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002544:Cerebral Infarction / Q000150:complications*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics; D016291:Dizocilpine Maleate / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D005260:Female; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D017874:Immediate-Early Proteins; D009130:Muscle, Smooth / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000235:genetics*; D018696:Neuroprotective Agents / Q000494:pharmacology; D011149:Pons / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000235:genetics; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics; D001745:Urinary Bladder Diseases / Q000209:etiology* / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014157:Transcription Factors; D016291:Dizocilpine Maleate; D010959:Tissue Plasminogen Activator