Effect of Treadmill Running on c-Fos Expression in the Ventrolateral Periaqueductal Gray and Nucleus Raphe Magnus Regions of the Streptozotocin-Induced Diabetic Neuropathic Pain Mice

Il-Soo Lee,Young-Je Sim,Jee-Youn Kim,Il-Gyu Ko,Bo-Kyun Kim,Chang-Ju Kim,Choong-Yeol Lee 대한스트레스학회 2009 스트레스硏究 Vol.17 No.3

포유동물의 신경계에는 중심회백질과 큰솔기핵을 포함하는 하행성 진통작용이 있다. 만성 당뇨성 신경병증은 하행성 진통작용을 감소시켜 통증을 더욱 유발시킨다. c-Fos는 여러 자극에 의하여 발현이 증가되는데, 따라서 c-Fos의 발현은 신경의 흥분성을 나타낸다. 중심회백질과 큰솔기핵에서의 c-Fos 발현은 하행성 진통작용이 활성화 됨을 의미한다. 본 실험에서는 streptozotocin에 의하여 당뇨가 유발된 생쥐의 중심회백질과 큰솔기핵에서 c-Fos 발현에 미치는 트레드밀 달리기의 효과를 연구하였다. 달리기군은 하루 30분씩 30일간 트레드밀 달리기를 실시하였다. 당뇨가 유발된 생쥐의 중심회백질과 큰솔기핵에서 c-Fos 발현이 감소하였고, 인슐린 처치 또는 트레드밀 달리기를 실시한 결과 이러한 c-Fos 발현이 증가되었다. 본 실험의 결과 트레드밀 달리기는, 인슐린치료와 마찬가지로, 중심회백질과 큰솔 기핵의 신경을 흥분시켜 하행성 진통작용을 활성화 시킴으로써 당뇨성 신경병증의 증상을 경감시킴을 나타낸다. The mammalian nervous system contains descending pain control system, such as periaqueductal gray (PAG) and nucleus raphe magnus (NRM). In chronic diabetic neuropathic pain, the activity of descending pain control system may be reduced, further amplifying pain perception. c-Fos protein is rapidly expressed in neurons in response to various stimuli, and c-Fos expression is recognized as a marker of increased neuronal activity. Upregulations of c-Fos expression in the ventrolateral PAG (vlPAG) and NRM suggests the activation of descending pain control system. In the present study, we investigated the effect of treadmill running on the expression of c-Fos in the vlPAG and NRM regions of brains in the streptozotocin (STZ)-induced diabetic mice. Mice in the treadmill exercise group were forced to run on treadmill for 30 min once a day for 30 consecutive days. In mice with STZ-induced diabetes, the expression of c-Fos in the vlPAG and NRM was suppressed. Treadmill running, as like as insulin treatment, significantly increased c-Fos expression in the vlPAG and NRM. These results suggest that treadmill running might activate neurons in the vlPAG and NRM, and thus it alleviate the diabetes-related neuropathic pain through activation of descending pain control system. (Korean J Str Res. 2009;17:307∼312)

치아이동에 의한 백서 삼차신경감각핵군내 c-Fos의 발현

민경호,박효상,배용철,성재현 대한치과교정학회 1998 대한치과교정학회지 Vol.28 No.3

이 연구의 목적은 말초조직에 유해 자극을 가하였을 때 중추 신경계내 이차 신경 세포체내에 발현되어 Neuronal marker로 사용되고 있는 c-fos를 사용한 면역 조직화학법으로 치아이동시 동반되는 동통의 투사경로의 이해에 도움을 주고자하는 것이다. 생후 9 주령의 210gm내외의 Sprague-Dawley계 웅성 백서 21마리를 교정력을 가하지 않고 마취만을 시행한 정상대조군과 교정력 적용 시간 경과에 따라 1시간, 3시간, 6시간, 12시간, 1일, 3일군으로 나누어 각 해당 시간동안 상악 우측 제1대구치와 상악 우측 측절사이에 Ni-Ti coil spring을 결찰하여 30gm내외의 지속적인 교정력을 가한 후 희생시켰다. 희생시킨 백서의 뇌간을 적출하여 토끼의 항체를 이용하여 면역화학 염색을 시행하였다. 삼차신경 감각핵군내 부위에 따른 c-fos 면역 반응 세포를 측정하여 교정력 적용 시간 경과에 따른 변화를 관찰하였다. · c-fos면역 반응 세포의 배측에서의 분포는 자극측 중위핵과 미측핵의 이행부위에서 시작하여 제1경추 척수 후각에까지 이어졌는데 가장 많은 분포를 보인 곳은 미측핵의 문측 부위였다. 그리고 주로 I층 과 II층에서 관찰되었다. · 복측에서의 c-fos 면역 반응 세포의 분포는 자극측 중위핵의 미측 부위에서 시작하여 미측핵의 중간부위에 까지 이어졌다. · 교정력 적용 3,6시간군에서 c-fos면역 반응 세포가 가장 많이 관찰 되었으며 12시간군에서 감소되기 시작하여 1일, 3일군에서는 현저히 감소 하였다. 위로 미루어 볼 때 지속적인 교정력에 의한 동통은 중위핵과 미측핵의 이행부위, 미측핵, 제1경추 척수후각에서 매개되는 것으로 생각된다. The c-fos is known as neuronal marker of second neurons which is activated by noxious peripheral stimulation. To investigate the changes of c-fos expression in the trigeminal nucleus complex during tooth movement, immunohistochemical study was performed. Experimental rats(9 weeks old, 210 gm, 21 rats) were divided into seven groups(normal, 1 hour group, 3 hour group, 6 hour group, 12 hour group, 1 day group, 3 day group). Rats in the normal group were anesthesized without orthodontic force. Rats in the experimental groups were applied orthodontic force (approximately 30 gm) to upper right maxillary molar. Frozen sections of brain stem were immunostained using rabbit antisera. The change of c-fos expression were observed with respect to rostrocaudal distribution, laminar organization, and duration of orthodontic force application. The study results were as follows. · The c-fos nuclei in the dorsal part were observed from ipsilateral transition zone of subnucleus interpolaris and subnucleus caudalis to C1 cervical dorsal horn rostrocaudally. The maixmal peak point was the rostral part of subnucleus caudalis. The greatest proportion of c-fos cells were located within lamina and I and II. · The c-fos nuclei in the dorsal part were observed from the most caudal part of subnuleus interpolaris to the middle part of the subnucleus caudalis. · The number of c-fos immunoreactive dot increased at 1 hour group, reached its maximum at the 3 and 6 hour groups, and showed a decreasing trend after 12 hours. These resutls imply that nociceptive stimulation caused by continuous orthodontic force might be modulated by transition zone of subnucleus interpolaris and subnucleus caudalis, subnucleus caudalis, C1 spinal dorsal horn.

경련유발자극이 흰쥐 뇌에서 heat shock protein72 유전자발현에 미치는 영향

김현,김창미,강윤희,유임주,박재현,서영석 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.4

허혈성 신손상후 c - fos 및 Epidermal Growth Factor 유전자 발현양상

차대룡(Dae Ryong Cha),이영호(Young Ho Lee),장미경(Mi Kyung Jang),김난희(Nan Hee Kim),구자룡(Ja Ryong Koo),권영주(Young Joo Kwon),조원용(Won Yong Cho),김형규(Hyoung Kyu Kim),김창수(Chang Soo Kim) 대한내과학회 1994 대한내과학회지 Vol.47 No.6

N/A Objectives: Acute renal failure (ARF) is a syndrome that can he broadly defined as rapid deterioration of renal function resulting in the accumulation of nitrogenous wastes such as urea and creatinine. The incidence of ARF will most likely increase in the future as a predictable by-product of the continuous advances in surgical techniques and pharmacotherapy. The severity of renal dysfunction after ARF depends on the exent of the initial renal damage as well as the pace of repair process, and the regeneration of tubular epithelial cell is essential in the recovery of ARF. Recently several studies reveal the importance of specific growth factor such as epidermal growth factor (EGF), transforming growth factor-alpha (TGFα) and the expression of these genes is increased during the recovery stage of ARF. To evaluate the expression of c-fos and EGF genes involved in cellular proliferation during acute ischemic renal failure, author performed the northern and dot hybridization of renal tissue at different reperfusion time in the ischemic ARF rats. Methods: The experimental animals were divided into three groups. Group I (n=3) was control without any procedure, group II (n=3) was sham operation group (bilateral flank incision and decapsulation were made without renal artery clamping), group III (n=15) was ischemic ARF model by right nephrectomy and left renal artery clamping for 40 minutes. In ischemic group (Group III), rats were divided into three subgroups according to reperfusion time such as 1, 24, 72 hours (IIIa, IIIb, IIIc in each). For these studies, the non-ischemic right kidney removed at the time of initial surgery served as a paired control. Becaus of inter-animal variation in mRNA content for specific genes, five rats were included for each time period. In all cases, whole blood were collected for measurement of serum creatinine at each reperfusion time. Total renal RNA was purified from intact whole kidneys by deproteinization with guanidinium isothiocyanate and phenol/chloroform/isoamyl alcohol. After the isolation of RNA, electrophoresis were done in a 1% agarose gel containing 20 mM MOPS, 1 mM EDTA, 5 mM Na acetate PH 7.0 and 2.2M formaldehyde and confirmed the intact RNA by the 18 S and 28 S ribosomal RNA. RNA was transferred to nylon membrane via vaccum transfer and then hybridization were performed at 65℃ with isotope labelled probes for 24hours, Autoradiographs were obtained and quantitated by computer-assisted dual- wave length flying spot scanner (CS-9000) at 530 nm. Results: In the control group, the serum creatinine was 0.9±0.2 mg/dl; in the sham operation group 0.8±0.3 mg/dl; in the ischemic group after 1 hour reperfusion, the serum creatinine was 0.9±0.3 mg/dl; In the ischemic group after 24hous and 72 hours reperfusion, the serum creatinine was 1.9±0.5 mg/dl and 3.6±1.4 mg/dl respectively. The mean serum creatinine level was statistically significant between control and post-ischemic 24, 72 hours reperfusion group (p<0.05). c-fos gene was rapidly induced by renal ischemia with peak after 60 minutes of reflow and 24 hours later c-fos message was markedly decreased. The expression of c-fos gene was. more markedly increased in the more severe ischemic injury. EGF gene expression was markedly decreased after 1 hour of reflow and substantially increased in activity ?2 hours after ischemia. Conclusion: From the above findings, c-fos gene expression is rapidly induced by ischemia and this gene expression is essential in the recovery phase of acute ischemic renal failure. EGF gene expression substantially increased in activity is probablely associated with renal epithelial cell proliferation. Although the specific roles of c-fos and EGF genes in tissue recovery are not known, the expression of these genes may be play an important role in the recovery phase of acute ischemic renal failure.

한우 c-fos 유전자의 염기서열 및 발현분석

유성란,정행진,정기철,이준헌,조규완,최재관,나기준,상병찬 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.6

Cellular FOS(c-fos) protein is a transcription factor that forms heterodimers mostly with c-jun family and stimulates the transcription of genes containing AP-1 regulatory elements. This c-fos expression can control growth and differentiation of various precursor cells including myoblasts. The controls by c-fos gene have been identified for affecting skeletal muscle fiber traits which are the key determinants of meat quality in pigs. As a first step for identifying the relationship between c-fos gene and meat quality traits in cattle, we fully sequenced 1,443 bp of Hanwoo c-fos mRNA and analyzed expression patterns from various organs and muscle tissues. The sequence identities of Hanwoo c-fos with that of human, pig and mouse showed 89.8%, 93.3% and rib muscle from 7 organs and 9 different parts of muscles investigated. These results presented here can be used as a valuable marker for meat quality related traits in cattle with further verification.

흰쥐 해마에서 수영운동이 c-fos, c-jun 발현에 미치는 영향

이성호(Sung-Ho Lee) 한국콘텐츠학회 2011 한국콘텐츠학회논문지 Vol.11 No.1

본 연구는 흰쥐 해마에서 c-fos, c-jun 발현에 수영운동이 미치는 영향을 규명하는 것이다. 실험 대상은 생후 4주 흰쥐(4-weeks aged rat)와 생후 4개월 흰쥐(16-weeks aged rat)를 사용하였다. 두 집단 모두 대조군, 실험군으로 분류하였으며, 수영 운동은 1일 1시간 하였으며 1, 3, 7일 실시한 후 다음과 같은 결과를 얻을 수 있었다. c-fos, c-jun 단백질 발현에 있어서 두 실험군 모두 운동 1, 3, 7일에서 유의하게 증가하였으며, 7일이 가장 많이 증가하였고 3일, 1일 순으로 증가 하였다. 두 실험군을 비교했을 때 생후 4주 그룹이 4개월 그룹보다 더 많은 c-fos, c-jun 단백질 발현을 보여 통계적으로 유의하게 나타났다. 따라서 수영 운동이 해마에서 c-fos, c-jun 단백질 발현을 증가시키는 것으로 나타나 운동의 효과가 있는 것으로 보이며, 수영 운동에 의한 초기발현 유전자의 활성화로 인하여 학습 및 기억과 같은 인식기능을 예방 및 개선시키며 신경성장 및 회복에 긍정적인 효과가 있는 것으로 보인다. This study is to examine the effect of swimming exercise on the expression of c-fos, c-jun protein in rat hippocampus. 4-weeks aged rats and 16-weeks aged rats were used in experimental materials. All of two groups were classified into control and swimming exercise group. Swimming exercise was practiced for an hour a day. The results were got as follows after practical application in 1 day, 3days, 7 days. The expression of c-fos, c-jun protein was increased in all of the two experimental groups significantly in 1 day, 3days, 7 days. It was increased gradually in order of after 1 day, 3days, 7 days. There seems to be the effect of swimming exercise increasing the expression of c-fos, c-jun protein in hippocampus. Therefore swimming exercise can improve cognitive function such as learning and memory and prevent through activating immediate - early gene by swimming exercise. And it seems to have the positive effect on growth and recovery of nerve.

자연과학편 : 트레드밀 운동이 당뇨 흰쥐에서 태어난 새끼 쥐의 해마 c-Fos 발현에 미치는 영향

백성수(SeungSooBaek),전태원(TaeWonJun),조한샘(HanSamCho),이희혁(HeeHyukLee),윤진환(JinHwanYun),신말순(MalSoonShin),김창주(ChangJuKim) 한국체육학회 2006 한국체육학회지 Vol.45 No.5

임신 중 당뇨는 태아의 육체적 발육 및 정신적 발육에 해로운 영향을 미쳐, 출산 후 뿐만 아니라 그 아이가 성인이 되어서도 정서적 발달과 정신적 발달에 큰 영향을 야기할 수 있다. 본 연구는 당뇨가 유발된 어미쥐에서 태어난 새끼 쥐들에서 트레드밀 운동이 신경세포 활성에 미치는 효과를 알아보는 데 목적이 있다. Sprague-Dawley 계 흰쥐 임신 1주째에 streptozotocin(STZ)를 투여하여 당뇨를 유발하였으며, 이들 쥐에서 태어난 생후 28일 째인 어린 쥐들에게 2주간 트레드밀 운동을 적용하였다. 본 실험 결과 임신 중 당뇨 유발은 새끼 쥐 해마에서 c-Fos 발현을 억제시킴으로써 임신 중 당뇨로 인하여 새끼 쥐들의 신경발달학적 손상을 유발시켰으며, 새끼 쥐들의 트레드밀 운동은 c-Fos의 발현을 정상치까지 증가 시켰다. 본 실험을 통하여 트레드밀 운동은 당뇨에 의한 신경세포 활성의 억제를 치유하는데 유용한 대안이 될 수 있을 것으로 사료된다. Diabetes mellitus during pregnancy exerts a detrimental effects on the development of the fetus and its central nervous system. However, little is known about the effect of maternal diabetes on hippocampal c-Fos expression. In the present study, the influence of postnatal treadmill exercise on hippocampal c-Fos expression in the rat pups born from the maternal rats with streptozotocin(STZ)-induced diabetes was investigated. Pregnant rats were divided into two groups: the control group and the STZ-injection group. Rat pups were divided into four groups: the control group, the control with postnatal exercise group, the STZ-injection group, and the STZ-injection with postnatal exercise group. Treadmill exercise was started on the 28th day after birth for 2 weeks. The rat pups born from the maternal rats with diabetes showed decreased c-Fos expression in the hippocampus, whereas postnatal treadmill exercise increased c-Fos expression in the rat pups born from the maternal rats with diabetes. Based on the present results, it can be suggested that postnatal treadmill exercise may be useful in the treatment of neurodevelopmental problems in children born from the mothers who have experienced diabetes during pregnancy.

Swimming during pregnancy increases the expression c-Fos and c-Jun in the hippocampus of rat offspring

심영제,김지연,김창주 한국운동영양학회 2009 Physical Activity and Nutrition (Phys Act Nutr) Vol.13 No.1

The expression of c-Fos and c-Jun represents neuronal activity and plays a crucial role in the shaping of the development of brain. During the late pregnancy, exercise is known to influence neuronal activity of offspring. In the present study, the effect of swimming during pregnancy on the expression of c-Fos and c-Jun in the CA1, CA2, CA3 regions, and the dentate gyrus of the hippocampus of rat offspring was investigated using immunohistochemistry. Pregnant rats in the swimming group were forced to swim for 10 min once a day from 15 days after pregnancy until delivery. The expression of c-Fos and c-Jun in the CA1, CA2, CA3 regions, and the dentate gyrus of the hippocampus of pups was significantly increased by maternal swimming during late pregnant period. The present results show that prenatal swimming may enhance the neuronal activity of pups and affect the neonatal brain development.

초음파 조사에 의한 좌골신경 손상된 랫드 요척수부에서의 c-fos 발현양상

김영철(Young-Chul Kim),김동대(Dong-Dae Kim),김진상(Jin-Sang Kim) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.2

To evaluate the effects of low-intensity ultrasound application to sciatic nerve injured rats on c-fos expression in the lumbar spinal cord, various continuous-wave ultrasound treatments with intensities of 0.2 W/㎠, 0.5 W/㎠ and 1.0 W/㎠ operated at 1 ㎒ or sham treatment were applied to the opposite inside of the nerve injury site for 1 minute every other day with a transducer moving speed of 2 ㎝/sec. c-Fos expression was markedly increased at 1hour after sciatic nerve injury, then gradually decreased thereafter. c-Fos expressions were significantly decreased (p < 0.05) in all the experimental groups in comparison with the control group until 3days post-injury, and the degrees of decrease were higher in 0.5 W/㎠ and 1 W/㎠ intensity ultrasound application groups. However, no significant difference in c-fos expressions was observed between the experimental groups and the control group after 7 days post-injury. Therefore, it is suggested that low-intensity ultrasound application after peripheral nerve injury suppresses a pain transmission.

침자(鍼刺)가 혈압(血壓) 및 신경계(神經系) 혈압중추(血壓中樞) c-fos 발현에 미치는 영향(影響)

강동환 ( Dong Hwan Kang ),윤여충 ( Yeo Chung Yun ),김정상 ( Jeong Sang Kim ),김원재 ( Won Jae Kim ),라창수 ( Chang Su Na ) 대한경락경혈학회 2002 Korean Journal of Acupuncture Vol.19 No.1

The frequency of the hypertension is increasing as the life level is improved and an average span of the life is extended since we approached modern stage. The hypertension is also dangerous disease which raises fatal complication for example with the bleeding aproplexy and the ischemic attack. The medicinal treatment about the hypertension is required patients to take continually. The acupuncture have been introduced because a medicine-chemical treatment hasn`t good influence on the human body. It recently has been processed that studies acupuncture effect for blood pressure and have been found out that blood pressure go down. The object of this study observe the effect of LR3 acupuncture on hypertension in Renal Hypertension RAT induced by 2K1C. The 2K1C model was based on renin-angiotensin system. We put the silver clip in renal artery to induce renal hypertension. We try to observe that LR3 acupuncture influence on the blood pressure and c-fos expression in CVLM, NTS, RVLM. In results, the blood pressure was decreased during acupuncture than before acupuncture, after acupuncture. The heart rate was also decreased during acupuncture than before acupuncture, after acupuncture. The LR3 acupuncture significantly effects on blood pressure and heart rate (P<0.05). The increased expression of c-fos was shown in CVLM, NTS, but not in RVLM. In conclusion, LR3 was relived the action of control upon the hypertension and related with medulla, particularly CVLM, NTS. It needs to be closely examined pharmacological mechanism and studied combination with other acupoints.