지구성 유산소 운동이 모체감염으로 유발된 뇌성마비 새끼 쥐 해마의 세포사멸에 미치는 영향
Effects of endurance aerobic exercise on apoptosis in the hippocampus of the rat pups with maternal infection-induced cerebral palsy
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본 연구는 모체 감염으로 인한 뇌성마비 새끼 쥐들에게 지구성 유산소 운동인 수영 또는 트레드밀 달리기를 실시하였다. 뇌성마비 유발을 위하여 임신 15, 17, 20일에 kg당 0.15 mg의 lipopolysacchardie를 0.9% 생리식염수에 용해하여 마리당 1 ml의 양으로 복강에 주사(intraperitoneal injection)하였다. 정상 어미 쥐와 lipopolysacchardie를 복강에 주입한 어미 쥐에서 출산한 새끼 쥐들은 각각 대조군, 뇌성마비 유발군, 뇌성마비 유발 후 수영 운동군, 뇌성마비 유발 후 트레드밀 운동군으로 나누었다 (각 군 5마리씩). 생후 12주차부터 매일 30분씩 주당 5회의 지구성 유산소 운동인 수영 또는 트레드밀 운동을 총 2주간 실시하였다. 본 실험의 결과, 모체감염으로 뇌성마비를 유도시킨 새끼 쥐들의 해마에서 세포사멸을 억제하는 단백질인 Bcl-2의 발현은 감소되었고, 세포사멸을 촉진하는 단백질인 Bax, caspase-3, Fas, cytochrom c의 발현들은 증가하였다(p<.05). 수영 또는 트레드밀 운동을 실시한 새끼 쥐들에서는 Bcl-2의 발현이 항진된 반면 Bax, caspase-3, Fas, cytochrom c의 발현들은 억제되었다(p<.05). 본 실험의 결과 지구성 유산소 운동은 모체감염으로 유발된 뇌 손상 치료에 도움이 되는 치료법으로 생각되어진다.
Abstract
In the present study, we investigated the effects of endurance aerobic exercise, swimming or treadmill running, on apoptosis in the hippocampus of the rat pups with maternal infection-induced cerebral palsy (CP). CP in the neonatal rats was induced by intraperitoneal injection of 0.15 mg/kg lipopolysaccharide to the pregnant rats at gestation day 15, 17, and 20. The neonatal rats were divided into four groups: the control group, the CP-induction group, the CP-induction and swimming group, and the CP-induction and treadmill running group (n = 5 in each group). After 12 weeks of birth, the rat pups in the swimming group and in the running group were made to perform each exercise for 30 min once a day for 5 times per week during 2 weeks. The rat pups with CP showed decreased expression of anti-apoptotic protein Bcl-2, while increased expressions of pro-apoptotic proteins Bax, caspase-3, Fas, and cytochrom c(p<.05). Swimming or treadmill running, enhanced Bcl-2 protein expression, in contrast, suppressed Bax, caspase-3, Fas, and cytochrom c expressions in the hippocampus of the rat pups with cerebral palsy(p<.05). The present study revealed that endurance aerobic exercise is helpful intervention for the treatment of maternal infection-induced brain damage.
참고문헌 (38)
- 김기정, "트레드밀 운동이 모체감염으로 유발된 뇌손상 새끼 쥐의 해마에서 cyclooxygenase-2 발현과 신경세포사에 미치는 영향", 한국체육학회지, 47(2), pp.383~389 (2008), 한국체육학회
- Back, S, "Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury", Journal of Neuroscience, 21, pp.1302~1312 (2001)
- Brooks, G. A, "Determination of metabolic and heart rate responses of rats to treadmill exercise", Journal of Applied Physiology, 45(6), pp.1009~1015 (1978)
- Bush, J. A, "The role of Bcl-2 family members in the progression of cutaneous melanoma", Clinical & Experimental Metastasis, 20, pp.531~539 (2003)
- Chang, H. K, "Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells", Biological & Pharmaceutical Bulletin, 29(8), pp.1597~1602 (2006)
- Cory, S, "The Bcl-2 family: Roles in cell survival and oncogenesis", Oncogene, 22, pp.8590~8607 (2003)
- Dammann, O, "Perinatal infection, fetal inflammatory response, white matter damage and cognitive limitations in children born preterm", Mental Retardation and Developmental Disabilities Research Reviews, 8, pp.46~50 (2002)
- Debatin, K. M, "Apoptosis pathways in cancer and cancer therapy", Cancer Immunol Immunother, 53, pp.153~159 (2004)
- Eskes, R, "Bax-induced cytochrome c release from mitichondria is independent of the permeability transition pore but highly dependent on Mg2+ ions", Journal of Cell Biology, 143, pp.217~224 (1998)
- Girard, S, "Developmental motor deficits induced by combined fetal exposure to lipopolysaccharide and early neonatal hypoxia", ischemia: A novel animal model for cerebral palsy in very premature infants, 2009, pp.158, 673~682
- Green, D. R, "Overview: apoptotic signaling pathways in the immune system", Immunological Reviews, 193, pp.5~9 (2003)
- Hargitai, B, "Apoptosis in various organs of preterm infants: histologic study of lung, kidney, liver and brain of ventilated infants", Pediatric Research, 50, pp.110~114 (2001)
- Hengartner, M. O, "The biochemistry of apoptosis", Nature, 407, pp.770~777 (2000)
- Johansson, B. B, "Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat", Experimental Neurology, 139(2), pp.322~327 (1996)
- Kim, H, "The influence of maternal treadmill running during pregnancy on short-term memory and hippocampal cell survival in rat pups", International Journal of Developmental Neuroscience, 25(C), pp.243~249 (2007)
- Kinney, H. C, "Human oligodendroglial development: relationship to periventricular leukomalacia", Seminars in Pediatric Neurology, 5, pp.180~189 (1998)
- Korsmeyer, S. J, "Regulators of cell death", Trends in Genetics, 11, pp.101~105 (1995)
- Kuwana, T, "Bid, Bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane", Cell, 111, pp.331~342 (2002)
- Laurin, D, "Physical activity and risk of cognitive impairment and dementia in elderly persons", Archieved Neurology, 58, pp.498~504 (2001)
- Lee, H. H, "Marternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups", Brain & Development, 28, pp.147~154 (2006), 147-154.
- Li, H, "Deciphering the pathways of life and death", Current Opinion in Cell Biology, 11, pp.261~266 (1999)
- Liu, H. C, "Dual effects of morphine on permeability and apoptosis of vascular endothelial cells: morphine potentiates lipopolysaccharide-induced permeability and apoptosis of vascular endothelial cells", Journal of Neuroimmunol, 146(1), pp.13~21 (2004)
- Nagata, S, "The Fas death factor", Science, 267(5203), pp.1449~1456 (1995)
- Oltvai, Z. N, "Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death", Cell, 74, pp.609~619 (1993)
- Puthalakath, H, "Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins", Cell Death and Differentiation, 9, pp.505~512 (2002)
- Schendel, D, "Public health issues related to infection and pregnancy and cerebral palsy", Mental Retardation and Developmental Disabilities Research Reviews, 8, pp.39~45 (2002)
- Sharangpani, A, "Caspase activation in fetal rat brain following experimental intrauterine inflammation", Brain Research, 1200, pp.138~145 (2008)
- Shimizu, S, "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC", Nature, 399, pp.483~487 (1999)
- Shiraki, K, "Expression of Fas ligand in liver metastases of human colonic adenocarcinomas", Proceedings of the National Academy of Sciences of the United States of America, 통권 : 94, pp.6420~6425 (1997)
- Sim, Y. J, "Effect of postnim,l treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers", Brain & Development, 30(2), pp.118~125 (2008), 118-125.
- Sim, Y. J, "Long-term treadmill exercise overcomes ischemia-induced apoptotic neuronal cell death in gerbils.Physiology & Behavior", Physiology & Behavior, 84(5), pp.733~738 (2005)
- Steller, H., "Mechanisms and genes of cellular suicide", Science, 267, pp.1445~1449 (1995)
- Suda, T, "Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family", Cell, 75, pp.1169~1178 (1993)
- Suzuki, A, "Down regulation of Bcl-2 is the first step on Fas-mediated apoptosis of male reproductive tract", Oncogene, 13(1), pp.31~37 (1996)
- Tsujimoto, Y, "Involvement of the bcl-2 gene in human follicular lymphoma", Science, 228, pp.1440~1443 (1985)
- Tsujimoto, Y, "Bcl-2 and Bcl-xL block apoptosis as well as necrosis: possible involvement of common mediators in apoptotic and necrotic signal transduction pathways", Leukemia, 11(3), pp.380~382 (1997)
- van Praag, H, "Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus", Nature Neuroscience, 2, pp.266~270 (1999)
- Wei, M. C, "Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death", Science, 292, pp.727~730 (2001)
