Possible Therapeutic Effect of Exercise for Incurable Diseases

고일규 대한배뇨장애요실금학회 2021 International Neurourology Journal Vol.25 No.S2

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생쥐 정소의 발생단계에 따른 Estrogen receptor alpha (ERα)의 발현분석

고일규,오영석,계명찬 한국발생생물학회 2012 한국발생생물학회 학술발표대회 Vol.31 No.-

남성의 체내에 미량의 estrogen이 존재하며, 정소와 부정소에 estrogen receptor(ERα, β)가 발현한다. Estrogen은 estrogen receptor를 통한 signaling을 통해 기능을 수행한다. 본 연구에서는 출생직후, 생후 1, 2, 4, 8주령의 생쥐 정소 및 부정소를 획득한 후 정량적 RT-PCR, Western blot, 면역조직화학법, image analysis를 통해 ERα의 발현을 분석하였다. 생쥐의 주령별 정소에서 ERα mRNA의 발현분석 결과, 정소에서는 신생부터 1주령까지 발현량이 급격히 증가하였으며, 4주령부터 약간 감소하였다. Western blot 결과, 출생 직후부터 생후 7일까지 급격히 증가하였고, 14일까지 높은 수준으로 발현하다가 이후 감소하였다. 면역조직화학법을 통한 ERα의 발현부위분석 결과, 정소에서 ERα 단백질은 주로 leydig cell과 peritubular cell에서 발현하였다. Image analysis를 통한 ERα 발현의 양적분석 결과, leydig cell에서 ERα는 출생 직후에 낮게 발현하다가 7일까지 급격히 증가하였고, 14일까지 높은 발현량을 유지하다가 이후 감소하였다. 이는 발생단계에 따른 남성호르몬 농도와 상반되는 결과로서, ERα의 발현이 leydig cell의 증식과 남성호르몬의 생성을 억제하는 것으로 추측할 수 있다. Peritubular cell에서 ERα는 출생 직후부터 생후 14일까지 꾸준히 증가하다가 이후에 급격히 감소하였다. ERα는 peritubular cell의 증식에도 관여하는 것으로 사료되며, 발생단계에서 leydig cell에 비해 peritubular cell의 증식이 먼저 완료되는 것으로 사료된다. 이를 종합하면, ERα는 정소에서 스테로이드형성 및 leydig cell/peritubular cell의 증식에 관여할 것으로 사료된다.

Effect of Treadmill Exercise on Leak-point pressure and Neuronal Activation in Brain of Rats with Stress Urinary Incontinence

고일규,김성은,김창주,정지헌,이삼준,김동희,이광염,김계환 대한배뇨장애요실금학회 2010 International Neurourology Journal Vol.14 No.3

Purpose: Stress urinary incontinence (SUI) commonly occurs in women, and it causes enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these exercise is also known to be effective for relieving thesymptoms of SUI, however,the efficacy and underlying mechanisms of exercise on SUI are poorly understood. In the present study, we investigated the effect of treadmill exercise on abdominal leak-point pressure and neuronal activity in the medial preoptic nucleus (MPA), ventrolateral periaqueductal gray (vlPAG), and pontine micturition center (PMC) following urethrolysis in rats. Materials and Methods: Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. After having undergone transabdominal urethrolysis to induce SUI, the rats were divided into three groups (n=6 in each group): a sham operation group, an SUI-induced group, and an SUI-induced and treadmill exercise group. The rats in the exercise group performed treadmill running for 30 min once a day starting 2 weeks after the induction of SUI and continuing for 4 weeks after surgery. For this study, determination of abdominal leak point pressure and immunohistochemistry for c-Fos in the brain were performed. Results: Induction of transabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. In contrast, abdominal leak point pressure was significantly improved by treadmill exercise. The expression of c-Fosin the MPA, vlPAG, and PMC, the brain areas relating to micturition, was enhanced by the induction of SUI, whereas treadmill exercise significantly suppressed SUI-induced c-Fos expression, suggesting that neuronal activation in the micturition centers was suppressed by treadmill exercise. Conclusion: The present results suggest that treadmill exercise may be an effective therapeutic modality for ameliorating the symptoms of SUI.

Treadmill Exercise Reduces Lipopolysaccharide-induced Apoptotic Neuronal Cell Death in the Hippocampus of the Young and Old Rats

고일규,이삼준,김성은,신말순,김창주 대한스트레스학회 2011 스트레스硏究 Vol.19 No.2

Systemic inflammation exerts detrimental effects on the various organs, especially on the central nervous system (CNS), and leading to multiple organ failure. Lipopolysaccharide (LPS) is a lipid-containing polysaccharide which is endotoxin and acts as important group-specific antigen. LPS induces immune activation, causes inflammation, and results in deterioration of cellular function. Hippocampal neurons are particularly susceptible to this LPS. Treadmill exercise is known to ameliorate neurologic impairment induced by various brain insults. In the present study, we investigated the effects of treadmill exercise on short-term and spatial memories in relation with apoptotic neuronal cell death in the hippocampus following LPS-induced systemic inflammation. For the evaluation of age-dependent effect of treadmill exercise on these parameters, we used both young-aged and old-aged rats. In the present results, aging process impaired short-term and spatial memories through increase of apoptosis in the hippocampus. Treadmill exercise alleviated aging-induced impairment of short-term and spatial memories and suppressed aging-induced apoptosis in the old-aged rats. LPS-induced systemic inflammation disturbed short-term and spatial memories with increased apoptosis in both young-aged and old-aged rats. Treadmill exercise alleviated LPS-induced impairment of short-term and spatial memories and suppressed LPS-induced apoptosis in both young-aged and old-aged rats. Here in this study, we showed that treadmill exercise may inhibit LPS-induced neuronal apoptosis, thus facilitates recovery of memory function following systemic inflammation. Concerning that aging process disturbs memory function by enhancing of apoptotic neuronal cell death, these effects of treadmill exercise may be more important in the elderly. (Korean J Str Res 2011;19:97∼105)

Add-on Therapy With the α-Blockers Tamsulosin and Naftopidil Improves Voiding Function by Enhancing Neuronal Activity in Prostatic Hyperplasia Rats

고일규,황락경,진준장,김상훈,한진희,전정원,조성태 대한배뇨장애요실금학회 2018 International Neurourology Journal Vol.22 No.1

Purpose: Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1- Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. Methods: Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression. Results: Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy. Conclusions: Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.

In Vitro Reconstruction of Brain Tumor Microenvironment

고일규,김필남 한국바이오칩학회 2019 BioChip Journal Vol.13 No.1

The cancer cells in brain tumors interact with their microenvironment, which includes stromal cells, the extracellular matrix (ECM), and the physical properties of tissues. The reciprocal interaction between cancer cells and the surrounding microenvironment regulates the biological behavior of cancer cells. To improve our understanding of the progression of brain tumors, it is useful to construct physiologically relevant brain tumor models. Consequently, versatile in vitro tumor models ranging from simplistic twodimensional (2D) cultures to three-dimensional (3D) cultures have been developed to mimic the microenvironments of the brain. This review covers the recent progress in the in vitro reconstruction of brain tumor microenvironments.

Therapeutic Strategies Against Apoptosis and Gliosis

고일규 대한배뇨장애요실금학회 2020 International Neurourology Journal Vol.24 No.S2

Effects of Combination Treatment of Alpha 1-Adrenergic Receptor Antagonists on Voiding Dysfunction: Study on Target Organs in Overactive Bladder Rats

고일규,문보민,김성은,진준장,황락경,지은상,김창주,김태형,최현희,정경진 대한배뇨장애요실금학회 2016 International Neurourology Journal Vol.20 No.S1

Purpose: Overactive bladder (OAB) causes urinary urgency, usually accompanied by frequency and nocturia. Alpha 1-adrenergic receptor (α1-AR) antagonists are known to improve lower urinary tract symptoms associated with OAB. The α1-AR antagonists constitute a variety of drugs according to the receptor subtype affinity. This study investigated the efficacy of tamsulosin, naftopidil, and a combination of the two on OAB rats. Methods: The OAB rat model was induced by an intraperitoneal injection of cyclophosphamide for 14 days. The experimental groups were divided into 5 groups: control group, OAB-induction group, OAB-induction and tamsulosin monotherapy group, OAB-induction and naftopidil monotherapy group, and OAB-induction and tamsulosin-naftopidil combination therapy group. For the drug-treated groups, each drug was administrated for 14 days after the OAB induction. Cystometry for urodynamic evaluation and immunohistochemical stain for c-Fos and nerve growth factor (NGF) expressions in the central micturition centers were performed. Results: Increased contraction pressure and time with enhanced c-Fos and NGF expressions in the central micturition centers were found in the OAB rats. Tamsulosin suppressed contraction pressure and time while inhibiting c-Fos and NGF expressions. Naftopidil showed no significant effect and combination therapy showed less of an effect on contraction pressure and time. Naftopidil and combination therapy exerted no significant effect on the c-Fos and NGF expressions. Conclusions: Tamsulosin showed the most prominent efficacy for the treatment of OAB compared to the naftopidil and combination. The combination of tamsulosin with naftopidil showed no synergistic effects on OAB; however, further studies of addon therapy might provide opportunities to find a new modality.

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

고일규,김성은,김보균,신말순,김창주,임성진,방유정,최인호,김계환 대한배뇨장애요실금학회 2011 International Neurourology Journal Vol.15 No.2

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.

생쥐 정소와 부정소 발생단계에 따른 estrogen receptor alpha (ERα)의 발현

고일규,이재은,오영석,계명찬 한국발생생물학회 2011 한국발생생물학회 학술발표대회 Vol.30 No.-

남성의 체내에 미량의 estrogen이 존재하며, 정소와 부정소에 estrogen receptor (ERα, β)가 발현한다. Estrogen은 ERα와 ERβ를 통해 세포의 생존, 증식 및 분화를 조절한다. ERα는 정소에서 스테로이드형성, 정자형성 부정소에서 정자 성숙 및 부정소 체액항상성 조절기능을 수행할 것으로 추측된다. 본 연구에서는 출생 직후, 생후 1, 2, 4, 8주령의 생쥐 정소 및 부정소를 획득한 후 정량적 RT-PCR, Western blot, 면역조직화학법을 이용하여 ERα의 발현을 확인하였다. 생쥐의 주령별 정소와 부정소에서 ERα mRNA의 발현분석 결과, 정소에서는 신생부터 1주령까지 발현량이 급격히 증가하였으며 4주령부터 약간 감소하였다. 부정소에서는 신생부터 4주령까지 비슷한 발현량을 보였으며, 8주령에서 발현량이 증가하였다. Western blot 결과, 8주령 부정소에서 efferent duct에서 가장 강하게 발현하였고, 부정소 체부에서 가장 적게 발현되었다. 면역조직화학법을 통한 ERα의 발현부위분석 결과, 정소에서 ERα 단백질은 주로 Leydig cell과 peritubular cell에서 발현하였다. 부정소에서는 efferent duct와 두부 부정소에서 가장 강하게 발현되었으며, 두부 부정소의 principal cell과 narrow cell에서 강하게 발현되었다. 체부 부정소에서는 basal cell과 clear cell에서 발현하였다. 미부부정소에서는 stromal cell에서 강하게 발현하였고, basal cell과 clear cell에서도 발현되었다. ERα는 정소에서 스테로이드형성 및 Leydig cell의 증식에 관여하며, 부정소에서 정자의 성숙 및 저장에 관여할 것으로 사료된다.