Impact of Several Types of Stresses on Short-term Memory and Apoptosis in the Hippocampus of Rats / 대한배뇨장애요실금학회지

PURPOSE: Stress has a deteriorating effect on hippocampal function. It also contributes to symptom exacerbation in many disease states, including overactive bladder and interstitial cystitis/bladder pain syndrome. We investigated the effects of various types of stresses (restraint, noise, and cold) on short-term memory and apoptosis in relation with corticotropin-releasing factor (CRF) expression. METHODS: Rats in the restraint stress group were restrained in a transparent Plexiglas cylinder for 60 minutes twice daily. Rats in the noise stress group were exposed to the 120 dB supersonic machine sound for 60 minutes twice daily. Rats in the cold stress group were placed in a cold chamber at 4degrees C for 60 minutes twice daily. Each stress was applied for 10 days. A step-down avoidance test for short-term memory, immunohistochemistry for caspase-3 expression, and western blot analysis for Bax and Bcl-2 expressions were conducted. RESULTS: Latency time was decreased and CRF expression in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were increased in all of the stress groups. The number of caspase-3-positive cells in the hippocampal dentate gyrus was increased and the expressions of Bax and Bcl2 in the hippocampus were decreased in all of the stress groups. CONCLUSIONS: All of the stress groups experienced short-term memory impairment induced by apoptosis in the hippocampus. The present results suggest the possibility that these stresses affecting the impairment of short-term memory may also induce functional lower urinary tract disorders.

Swimming: Effects on Stress Urinary Incontinence and the Expression of Nerve Growth Factor in Rats Following Transabdominal Urethrolysis / 대한배뇨장애요실금학회지

PURPOSE: Stress urinary incontinence (SUI) commonly occurs in women, and it has an enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these, exercise is known to be effective for the relief of symptoms of SUI; however, the efficacy and underlying mechanisms of the effect of exercise on SUI are poorly understood. We investigated the effect of swimming the symptom of SUI in relation to the expression of nerve growth factor (NGF) in rats. METHODS: Transabdominal urethrolysis was used to induce SUI, in Sprague-Dawley rats. The experimental groups were divided into the following three groups: sham-operation group, transabdominal urethrolysis-induced group, and transabdominal urethrolysis-induced and swimming group. The rats in the swimming group were forced to swim for 30 minutes once daily starting 2 weeks after SUI induction and continuing for 4 weeks. For this study, determination of abdominal leak point pressure and immunohistochemistry for NGF in the urethra and in the neuronal voiding centers (medial preoptic nucleus [MPA], ventrolateral periaqueductal gray [vlPAG], pontine micturition center [PMC], and spinal cord [L4-L5]) were performed. RESULTS: Transabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. Abdominal leak point pressure, however, was significantly improved by swimming. The expression of NGF in the urethra and in the neuronal voiding centers (MPA, vlPAG, PMC, and L4-L5) relating to micturition was enhanced by the induction of SUI. Swimming, however, significantly suppressed SUI-induced NGF expression. CONCLUSIONS: Swimming alleviated symptoms of transabdominal urethrolysis-induced SUI, as assessed by an increase in abdominal leak point pressure. The underlying mechanisms of these effects of swimming might be ascribed to the inhibitory effect of swimming on NGF expression.

Effects of Tadalafil on the Cerebral Ischemia-induced Apoptotic Neuronal Cell Death in Motor Cortex of Gerbils / 대한남성과학회지

PURPOSE: Cerebral ischemia leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor, and it has been used for the treatment of erectile dysfunction. In the present study, we investigated whether tadalafil has the protective effect on apoptotic neuronal cell death in the motor cortex following transient global ischemia in gerbils. MATERIALS AND METHODS: For this study, Mongolian gerbils were used for the experimental animals, and transient global ischemia was induced to the gerbils by occlusion of both common carotid arteries for 7 min. Gerbils were randomly divided into five groups (n=8 in each group): the sham-operation group, the cerebral ischemia-induced group, the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. Tadalafil-treated groups received tadalafil orally once a day for a 7 consecutive days, starting one day after surgery. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemistry for caspase-3 were performed for the detection of apoptotic neuronal cell death in the motor cortex. RESULTS: The number of TUNEL-positive cells was 21.45+/-3.69/section in the sham-operation group, 771.66+/-97.25/section in the cerebral ischemia-induced group, 688.44+/-81.35/section in the cerebral ischemia-induced and 0.1 mg/kg tadalafil-treated group, 295.66+/-36.34/section in the cerebral ischemia-induced and 1 mg/kg tadalafil-treated group, and 198.47+/-25.25/section in the cerebral ischemia-induced and 10 mg/kg tadalafil-treated group. In the present results, induction of ischemic injury increased apoptotic neuronal cell death in the motor cortex of gerbils. However, tadalafil treatment suppressed the cerebral ischemia-induced apoptotic neuronal cell death in the motor cortex as dose-dependently. CONCLUSIONS: Here in this study, we showed that tadalafil has protective effect on the cerebral ischemia-induced apoptotic neuronal cell death, and thus this drug may facilitate the recovery following ischemic cerebral injury.

Vardenafil Enhances Oxytocin Expression in the Paraventricular Nucleus without Sexual Stimulation / 대한배뇨장애요실금학회지

PURPOSE: Oxytocin is associated with the ability to form normal social attachments. c-Fos is an immediate early gene whose expression is used as a marker for stimulus-induced changes in neurons. The effect of phosphodiesterase-5 (PDE-5) inhibitors on oxytocin activation in the brain without sexual stimuli has not yet been reported. In the present study, we investigated the effects of vardenafil on oxytocin and c-Fos expression in the paraventricular nucleus (PVN) of conscious rats. METHODS: Male Sprague-Dawley rats weighing 300+/-10 g were divided into 6 groups (n=5 in each group): the control group, the 1-day-0.5 mg/kg, the 1-day-1 mg/kg, the 1-day-2 mg/kg, the 3-day-1 mg/kg, and the 7-day-1 mg/kg vardenafil administration group. The experiment was conducted without sexual stimulation. Vardenafil was orally administered. The animals in the control group received an equivalent amount of distilled water orally. The expression of oxytocin and c-Fos in the PVN was detected by immunohistochemistry. RESULTS: Oxytocin expression in the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil appeared in a duration-dependent manner. c-Fos in the oxytocin neurons of the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil also appeared in a duration-dependent manner. These results showed that vardenafil augments the expression of oxytocin with activation of oxytocin neurons in the PVN. CONCLUSIONS: In this study, we showed that the PDE-5 inhibitor, vardenafil directly enhances oxytocin expression and also activates oxytocin neurons in the PVN, which indicates that vardenafil may exert positive effects on affiliation behavior and social interaction.

Vardenafil Increases Cell Proliferation in the Dentate Gyrus through Enhancement of Serotonin Expression in the Rat Dorsal Raphe

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.