뇌 타박 손상 후 해마에서 신경세포 생성 및 신경가소성 조절 단백질 발현에 미치는 운동 기간에 따른 효과
Effects of Time Window for Exercise on Neurogenesis and Synaptic Plasticity-regulated Proteins in the Hippocampus after Traumatic Brain Injury
2
조회
0
다운로드
9
인용
0
참고문헌
키워드
초록
이 연구의 목적은 외상성 뇌손상 후 해마에서 신경세포 생성과 신경 가소성에 관여하는 단백질들에대한 운동 기간에 따른 효과를 규명하는 것이다. 이 연구에서는 7주령 Sprague-Dawley 계열의 수컷흰쥐(n=70)를 사용하여, 무선배치 방식으로 통제군(n=10), 외상성 뇌손상 대조군(7, 14 그리고 28일, n=10) 그리고 외상성 뇌손상 후 운동군(7, 14 그리고 28일, n=10)으로 분류하였다. 외상성 뇌손상은 electromagnetic controlled inpact 장비에 의해 유도되었다. 트레드밀 운동은 7, 14 그리고 28일동안 일주일에 5일, 하루에 30분씩 8m/min의 속도로 수행하였다. 외상성 뇌손상 후 손상 범위를 비교분석확인하기 위해 H&E 염색법을 수행하였고, 모든 그룹에서 통계적인 유의성은 나타나지 않았다. western blot을 수행하기 위해 모든 그룹에 해마를 적출하였다. 외상성 뇌손상 후 해마에서 BDNF, synapsin I 그리고 p-CREB의 발현은 정상군에 비해 감소하였지만, 손상 후 7, 14 그리고 28일 동안의 규칙적인 트레드밀운동은 BDNF, syanpsin I 그리고 p-CREB의 발현을 통계적으로 유의하게 증가시켰다. 또한 운동에 의한synapsin I과 p-CREB의 증가 패턴은 BDNF의 변화와 비슷한 경향을 보였다. 이러한 결과들을 종합해 볼때, 트레드밀 운동은 외상성 뇌손상 후 해마의 신경세포 생성 및 신경 가소성을 증가시키는 중요한 매개체임을알 수 있다.
Abstract
This study aims to investigate effects of time window for exercise on neurogenesis- and synaptic plasticity-regulated proteins in the hippocampus after traumatic brain injury (TBI). Male SD rats, aged 7weeks, were randomly assigned to the following three groups: Sham-operation group (n=10), TBI group (7, 14 and 28 days post injury, n=10) and TBI and exercise group (7, 14 and 28 days post injury, n=10). TBI was induced by a electromagnetic controlled impact. Treadmill exercise was conducted with duration and frequency of 30 minutes and 5 times per week, respectively, for 7, 14 and 28 days. H&E staining was used for comparing injury area in all TBI groups and there was not different significantly. Hippocampus in all groups was prepared and used for western blot. In our results, although TBI resulted in decrease of BDNF, synapsin I and p- CREB induction levels in hippocampus of the brain,exercise for 7, 14 and 28 days after TBI significantly enhanced expression levels of these proteins. Increase of synapsin I and p-CREB showed trendency similar to exercise-regulated BDNF. Based on the results, it can be suggested that treadmill exercise provide a beneficial effect on neurogenesis and synaptic plasticity in hippocampus of rat with TBI.
참고문헌 (35)
- Ashman,T.A, "Neurobehavioral consequences of traumatic brain injury", Mt Sinai J. Med, 73, pp.999~1005 (2006)
- Bigler,E.D, "Quantitative magnetic resonance imaging in traumatic brain injury", Head Trauma Rehabil, 16(2), pp.117~134 (2001)
- Binder,S, "The public health approach to traumatic brain injury:an overview of CDC's research and programs", J. Head Trauma Rehabil, 20, pp.189~195 (2005)
- Blaha,G.R, "Brain-derived neurotrophic factor administration after traumatic brain injury in the rat does not protect against behavioral or histological deficits", Neuroscience, 99(3), pp.483~493 (2000)
- Bourtchouladze,R, "Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein", Cell, 79, pp.59~68 (1994)
- Chen,S, "Time course of cellular pathology after controlled cortical impact injury", Exp Neurol, 182(1), pp.87~102 (2003)
- Conte,V, "TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice", Restor Neurol Neurosci, 26(1), pp.45~56 (2008)
- Dash,P.K, "Injection of the cAMPresponsive element into the nucleus of Aplysia sensory neurons blocks longterm facilitation", Nature, 345, pp.718~721 (1990)
- DeRidder,M.N, "Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition", Neurobiol Dis, 22(1), pp.165~176 (2006)
- Farmer,J, "Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo", Neuroscience, 124(1), pp.71~79 (2004)
- Finfer,S.R, "Severe traumatic brain injury", Resuscitation, 48(1), pp.77~90 (2001)
- Friedland,R.P, "Patients with Alzheimer’s disease have reduced activities in midlife compared with healthy control-group members", Proc. Natl. Acad. Sci. USA, 98, pp.3440~3445 (2001)
- Fujimoto,S.T, "Motor and cognitive function evaluation following experimental traumatic brain injury", Neurosci. Biobehav. Rev, 28, pp.365~378 (2004)
- Garcia,C.C, "Identification of a mutation in synapsin I,a synaptic vesicle protein,in a family with epilepsy", J Med Genet, 41(3), pp.183~186 (2004)
- Greengard,P, "Synaptic vesicle phosphoproteins and regulation of synaptic function", Science, 259(5096), pp.780~785 (1993)
- Griesbach,G.S, "Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent", J Neurotrauma, 24(7), pp.1161~1171 (2007)
- Griesbach,G.S, "Voluntary exercise following traumatic brain injury:brain-derived neurotrophic factor upregulation and recovery of function", Neuroscience, 125(1), pp.129~139 (2004)
- Hicks,R.R, "Vaccinia virus complement control protein enhances functional recovery after traumatic brain injury", J Neurotrauma, 19(6), pp.705~714 (2002)
- Hu,Z.G, "Ketogenic diet reduces cytochrome C release and cellular apoptosis following traumatic brain injury in juvenile rats", Ann Clin Lab Sci, 39(1), pp.76~83 (2009)
- Leker,R.R, "Cerebral ischemia and trauma-different etiologies yet similar mechanisms:neuroprotective opportunities", Brain Res Brain Res Rev, 39(1), pp.55~73 (2002)
- Li,L, "Impairment of synaptic vesicle clustering and of synaptic transmission,and increased seizure propensity,in synapsin I-deficient mice", Proc Natl Acad Sci U S A, 92(20), pp.9235~9239 (1995)
- Lie,D.C, "Neurogenesis in the adult brain:new strategies for central nervous system diseases", Annu Rev Pharmacol Toxicol, 44, pp.399~421 (2004)
- Lighthall,J.W, "Experimental models of brain injury", J. Neurotrauma, 6, pp.83~97 (1989)
- Llinás,R, "Regulation by synapsin I and Ca(2+)-calmodulin-dependent protein kinase II of the transmitter release in squid giant synapse", J Physiol, 436, pp.257~282 (1991)
- Melloni,R.H.Jr, "Dynamics of synapsin I gene expression during the establishment and restoration of functional synapses in the rat hippocampus", Neuroscience, 58(4), pp.683~703 (1994)
- Molteni,R, "Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray", Eur J Neurosci, 16(6), pp.1107~1116 (2002)
- Neeper,S.A, "Exercise and brain neurotrophins", Nature, 373(6510), pp.109~ (1995)
- Raghupathi,R, "Cell death mechanisms following traumatic brain injury", Brain Pathol, 14(2), pp.215~222 (2004)
- Seo,T.B, "Effect of treadmill exercise on Purkinje cell loss and astrocytic reaction in the cerebellum after traumatic brain injury", NEUROSCIENCE LETTERS, 481(3)(3), pp.178-182~182 (2010), ELSEVIER IRELAND LTD
- Van Praag,H, "Running enhances neurogenesis,learning,and longterm potentiation in mice", Proc. Natl. Acad. Sci. USA, 96, pp.13427~13431 (1999)
- Vaynman,S, "License to run:exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins", Neurorehabil Neural Repair, 19(4), pp.283~295 (2005)
- Vaynman,S, "Interplay between brain-derived neurotrophic factor and signal transduction ranulators in the regulation of the effects of exercise on synaptic-plasticity", Neuroscience, 122(3), pp.647~657 (2003)
- Wagner,A.K, "Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury", Exp Neurol, 195(2), pp.475~483 (2005)
- Wilde,M.C, "Cognitive impairment in patients with traumatic brain injury and obstructive sleep apnea", Arch. Phys. Med. Rehabil, 88, pp.1284~1288 (2007)
- Yin,J.C, "CREB as a memory modulator:induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila", Cell, 81, pp.107~115 (1995)