Naloxone Suppresses Exercise-induced Expression of Nitric Oxide Synthase in Rats Hypothalamus

김창주,이명화,박진국,김은경 대한스트레스학회 2004 스트레스硏究 Vol.12 No.4

Nitric oxide (NO)는 nitric oxide synthase (NOS)에 의하여 L-arginine으로부터 내재적으로 생성되는 기체로서, 식욕조절을 포함한 많은 생리적 기능을 수행하는 이차전령으로 잘 알려져 있다. 본 연구에서는 흰쥐 시상하부의 paraventricular nucleus와 ventromedial hypothalamic nucleus에서 opioid 길항제인 naloxone과 트레드밀 운동이 NOS의 발현에 미치는 영향을 연구하였다. 트레드밀 운동은 paraventricular nucleus와 ventromedial hypothalamic nucleus에서의 NOS의 발현을 증가시켰고, naloxone은 운동에 의하여 증가된 NOS의 발현을 억제하였다. 본 실험의 결과 내재적 opioid는 시상하부에서 운동에 의한 NOS 발현을 조절하고 있으며, 또한 운동이 식욕에 미치는 영향은 NOS에 의하여 조절됨을 알 수 있었다.

탈수가 모래쥐 시상하부에 출현하는 Vasopressin과 Oxytocin 분비신경세포에 미치는영향에 관한 면역조직화학적 연구

유기철,윤상선,남성안,조승묵,최창도,최월봉 대한해부학회 1997 Anatomy & Cell Biology Vol.30 No.6

노화흰쥐의 시상하부에서 vasopressin-면역반응 신경세포의 형태학적 변화

박영란(Young-Lan Park),정윤영(Yoon-Young Chung),천관영(Kwan-Young Cheon),박근용(Keun-Yong Park),설경수(Kyeong-Soo Seol),김종중(Jong-Joong Kim),문정석(Jeong Seok Moon) 대한체질인류학회 2007 해부·생물인류학 (Anat Biol Anthropol) Vol.20 No.1

노화는 중추신경계의 구조를 변화시킬 뿐 아니라 여러 신경인자들의 분포에 영향을 미쳐 생체리듬에 많은 변화를 초래한다. vasopressin (VP)은 시상하부에서 분비되는 펩타이드의 일종으로서, 주로 혈압을 상승시키고 항이뇨호르몬 작용을 가진다. 본 연구는 여러 생체리듬조절에 관여하는 시상하부에 분포하는 VP-면역반응 신경세포의 형태학적 변화를 노화흰쥐에서 관찰함으로써 노화로 인한 신경세포 변화를 관찰하고자 하였다. Sprague-Dawley계의 약 12주령인 젊은 흰쥐와 약 18월령의 노화흰쥐에 통상의 조직처리를 한 후 VP 일차항체를 사용하여 면역조직화학염색을 시행한 후 광학현미경으로 비교 관찰하였다. VP의 염색결과, VP-면역반응 신경세포는 주로 시상하부의 뇌실곁핵과 시각로위핵에서 두드러지게 관찰되었으며 노화흰쥐의 VP-면역반응 신경세포에서 핵과 세포체 크기가 젊은흰쥐에 비해 매우 크게 관찰되었으나 노화흰쥐의 VP-면역반응 신경세포의 수는 감소하였다. 그리고 시각교차위핵에서 노화흰쥐에서 VP-면역반응 신경세포의 수는 젊은흰쥐보다 약 2배정도 많이 나타났다. 따라서 노화가 진행됨에 따라 시상하부에서 VP 분비의 변화를 초래하여 다양한 기본생활주기가 달라지고 하루주기행동의 주간리듬(diurnal rhythm)의 변화에 영향을 미칠 것으로 사료된다. The role of neuropeptides in the central nervous system (CNS) has received increasing attention. Numerous peptide molecules are found in the mammalian CNS and many of them are thought to act as either neurotransmitters or neuromodulators. The neuropeptides found in high concentration in the hypothalamus include vasopressin (VP), vasoactive intestinal polypeptide, somatostatin, and oxytocin. The main approches to assess the involvement of neuropeptides can be focused on functions affecting the aging of the brain. Morphological aging of the CNS has been characterized by degenerative changes of fiber connections and cell loss, although degeneration does not always occur to the same extent throughout various parts of the brain and, moreover, varies for different cell types. Despite of many studies in VP containing neurons , there exist discrepancies in results about the changes of aged rat brain. The aim of the present study is, therefore, to investigative possible changes in the number and morphology of VPimmunoreactive neurons with aging in each area of the hypothalmus of the aged rats. As a result, the number of VP-immunoreactive neurons was decreased in hypothalamus nucleus of aged group. Especially, in VP-immunoreactive neurons of hypothalamus, the size of neuronal cell body and nuclei in aged group is larger than in young group and the fiber density of immunoreactivity neurons of median eminance (ME) in aged group is stronger than in young group. But, the total number of VP-immunoreactive neurons in the suprachiasmatic nucleus (SCN) of the aged group is larger than in the young group. These studies indicate the involvement of VP-immunoreactive neurons in aging process of hypothalamus, and aging process may affect the synthesis of VP in the neurons of hypothalamic nuclei. Whereas, in VP expression, aging process induces an enlargement of the cell size of surviving neurons to compensate.

운동 강도가 Lipopolysaccharide에 의하여 유도된 저강도 전신염증 흰쥐 모델에서 Tumor Necrosis Factor-α와 Interleukin-6 발현에 미치는 영향

김대영(Dae-Young Kim),김기정(Ki-Jeong Kim),성윤희(Yun-Hee Sung),서진희(Jin-Hee Seo),김성은(Sung-Eun Kim),김보균(Bo-Kyun Kim),이택현(Taeck-Hyun Lee),김창주(Chang-Ju Kim),김동희(Dong-Hee Kim),최현희(Hyun-Hee Choi) 대한스트레스학회 2010 스트레스硏究 Vol.18 No.3

본 연구의 목적은 lipopolysaccharide (LPS)에 의하여 유도된 저강도 전신염증 흰쥐 모델을 대상으로 유산소 운동 강도에 따른 혈청 및 뇌에서 종양 괴사 인자-알파와 인터루킨-6의 변화를 알아보고자 하였다. 본 실험에 사용된 동물은 Sprague-Dawley 수컷 흰쥐 45마리를 이용하였다. 실험동물은 open-field test 결과를 바탕으로 총 5개 군(각 군별 n=9)으로 배정하였다. 군의 구분은 대조군, LPS 투여군, LPS 투여 후 저강도 운동군, LPS 투여 후 중강도 운동군, LPS 투여 후 고강도 운동군으로 구성하였다. LPS 투여 후 트레드밀 운동은 경사도 0%에서 60분간 각 강도별로 일회실시하였다. 저강도 운동군은 8 m/min, 중강도 운동군은 14 m/min, 고강도 운동군은 22 m/min의 속도로 트레이드밀 달리기를 수행하였다. 본 실험의 결과 혈청의 종양 괴사 인자-알파(TNF-α)는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 운동군 모두에서 유의하게 감소하였다. 인터루킨-6(IL-6)는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 운동피질의 종양 괴사 인자-알파는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 모든 운동군에서 유의하게 감소하였다. 인터루킨-6는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 뇌실주위 신경핵에서의 종양 괴사 인자-알파는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 모든 운동군에서 유의하게 감소하였다. 인터루킨-6는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 본 연구의 결과, LPS 투여는 혈청 및 뇌 운동피질과 뇌실주위 신경핵에서 종양 괴사 인자-알파와 인터루킨-6의 발현을 증가시켰다. 또한 LPS 투여 후 고강도 운동은 혈청 및 뇌 운동피질과 뇌실주위 신경핵에서 종양 괴사 인자-알파를 억제하고 인터루킨-6의 발현을 증가시켰다. 본 실험의 결과 고강도 운동은 만성 질환의 원인인 저강도 전신염증의 개선에 보다 효과적인 것으로 나타났다. 따라서 저강도 전신염증 개선을 위한 운동강도 설정에는 고강도 운동이 보다 효과적일 수 있는 것으로 생각된다. In the present study, we investigated the effect of exercise intensity on the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the rats with lipopolysaccharide-induced low-grade systemic inflammation. Forty-five male Sprague- Dawley rats were used for the present study. The animals were divided into five groups (n=9 in each group): control group, LPS-treated group, LPS-treated and low-intensity exercise group, LPS-treated and moderate-intensity exercise group, and LPS-treated and high-intensity exercise group. Each training session consisted of one bout of treadmill running for 60 min at 0 degree of inclination. The exercise load of low-intensity was at a speed of 8 m/min, moderate-intensity was at a speed of 14 m/min, and high-intensity was at a speed of 22 m/min. In the present results, the concentrations of TNF-α and IL-6 in the serum were increased by LPS injection. The expressions of TNF-α and IL-6 in the motor cortex and hypothalamic paraventricular nucleus were also increased by LPS injection. Treadmill exercise at all intensities suppressed LPS-induced TNF-α levels in the serum, motor cortex, and hypothalamic paraventricular nucleus. Treadmill exercise at high-intensity enhanced IL-6 levels in the serum, motor cortex, and hypothalamic paraventricular nucleus. Our present study showed that high-intensity treadmill exercise decreased TNF-α level and increased IL-6 level in the serum, motor cortex, and hypothalamic paraventricular nucleus of rats with LPS-induced low-grade systemic inflammation. These results suggest that treadmill exercise at high-intensity may be valuable strategy for overcoming the low-grade systemic inflammation. (Korean J Str Res 2010;18:201∼208)

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

Shin, Seung-Yub,Han, Tae-Hee,Lee, So-Yeong,Han, Seong-Kyu,Park, Jin-Bong,Erdelyi, Ferenc,Szabo, Gabor,Ryu, Pan-Dong The Korean Society of Pharmacology 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.3

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by $x^2$-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

신승엽,한태희,이소영,한성규,박진봉,Ferenc Erdelyi,Gabor Szabo,류판동 대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.3

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11∼14%, p<0.01 by χ2-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

뇌실곁핵 (paraventricular nuclei)에서 탈수자극에 의한 neuropeptide 면역반응양상 변화

박인식(In-Sick Park),김진택(Jin-Taek Kim) 대한해부학회 1999 Anatomy & Cell Biology Vol.32 No.1

Dehydration induced an increase in plasma osmotic pressure that causes the release of the neurohypophysial hormone (Vasopresin, Oxytocin) which are synthesized in neurons of the paraventricular (PVN) and supra optic (SON) nuclei in the hypothalamus. On the other hand, PVN which plays an important role as an integration site for the neuroendocrine and autonomic nervous system neurons responded to osmotic stimulation. In this experiment, we studied that the change of several neuropeptidies (AVP: arginine vasopressin, CRF: corticotrophin releasing factor, GAL: galanin, NT: neurotensin. NPY: neuropeptide Y) immunoreactivity in the PVN according to the dehydration. The body weight of the rats decreased during dehydration and various changes were detected in hypothalamic neuropeptidies immunoreactivity.Our results show that: 1. Dehydration significantly increased AVP, CRF and GAL immunoreactivity in the PVN. 2. Dehydration slowly decreased NT immunoreactivity in the PVN. 3. NPY immunoreactive cell bodys were appeared during dehydration which did not observed in PVN at normal group. 인위적인 탈수자극이 뇌실곁핵 (paraventricular nuclei; PVN)에 존재하는 여러 신경전달물질 (arginine vasopressin; AVP, corticotropin releasing factor; CRF, galaine; GAL, neurotensin; NT, neuropeptide Y; NPY)의 분포양상에 어떤 영향을 미치는지를 조사하기 위해 면역조직화학적 기법을 이용하여 본 연구를 시행하였다. 실험동물은 체중 200 g 내외의 숫컷 흰쥐를 사용했으며 대조군과 7일동안 식수의 공급을 중지시킨 탈수군으로 나누어 시행한 결과 다음과 같은 결과를 얻었다. 탈수기간동안 실험동물의 체중은 급격하게 감소하여 탈수 7일군에서는 약 46%의 체중감소를 나타내었다. 1. 탈수자극에 영향을 받는다고 알려진 AVP, CRF 그리고 GAL 면역반응 양성신경세포와 신경섬유는 뇌실곁핵에서 실험 기간동안 계속하여 증가하는 경향이 관찰되었다. 2. 뇌실곁핵에서 NT 면역양성 세포체와 신경섬유는 탈수기간 동안 점차적으로 감소하였으며 7일군에서는 급속히 감소하 여 나타났다. 3. NPY 면역양성신경세포는 정상군에서는 신경섬유만이 나타났는데 탈수자극 7일군에서는 뇌실곁핵의 거대신경세포지역 (magnocellular part)에서 많은 신경세포체가 관찰되었다.

석고를 이용한 한국재래산양 시삭상핵과 방실핵의 입체적 재구성

이봉희,이흥식,이인세,이성준,Lee, Bong-hee,Lee, Heungshik S,Lee, In-se,Yi, Seong-joon 대한수의학회 1991 大韓獸醫學會誌 Vol.31 No.2

This study was carried out to reconstruct three-dimensional plaster model of the supraoptic and paraventricular nuclei of 3 Korean native goats. The representative coronal sections of the hypothalami were stained immunohistochemically with monoclonal antibodies to vasopressin and oxytocin simultaneously. Plaster models were reconstructed by schematic drawings which were made by tracing onto the tracing paper with the aid of a drawing attachment. The results were as follows: The configurations of the models of 3 supraoptic nuclei were slender spherical shape at their cranial parts, and the highest and widest size at middle parts, and became lower and narrow at caudal parts in two models, hence one was directed dorsolaterally. The medial surfaces of the para ventricular nuclei were vertically flat, and lateral surfaces were more complex than medial with processes directed dorsolaterally at their cranial portion. They change positions dorsally at caudal portion, and there were no significant variations in shape between them.

Differential activation of c-Fos in the paraventricular nuclei of the hypothalamus and thalamus following myocardial infarction in rats

Tae, Hyun-Jin,Park, Seung Min,Cho, Jeong Hwi,Kim, In Hye,Ahn, Ji Hyeon,Park, Joon Ha,Won, Moo-Ho,Chen, Bai Hui,Shin, Bich-Na,Shin, Myoung Cheol,Lee, Choong Hyun,Hong, Seongkweon,Lee, Jae-Chul,Cho, Jun D.A. Spandidos 2016 MOLECULAR MEDICINE REPORTS Vol. No.

<P>Proto-oncogene c-Fos (c-Fos) is frequently used to detect a pathogenesis in central nervous system disorders. The present study examined changes in the immunoreactivity of c-Fos in the paraventricular nucleus of the hypothalamus (PVNH) and paraventricular nucleus of the thalamus (PVNT) following myocardial infarction (MI) in rats. Infarction in the left ventricle was examined by Masson's trichrome staining. Neuronal degeneration was monitored for 56 days after MI using crystal violet and Fluoro-Jade B histofluorescence staining. Changes in the immunoreactivity of c-Fos were determined using immunohistochemistry for c-Fos. The average infarct size of the left ventricle circumference was ~44% subsequent to MI. Neuronal degeneration was not detected in PVNH and PVNT following MI. c-Fos immunoreactive (<SUP>+</SUP>) cells were infrequently observed in the nuclei of the sham-group. However, the number of c-Fos<SUP>+</SUP> cells was increased in the nuclei following MI and peaked in the PVNH and PVNT at 3 and 14 days, respectively. The number of c-Fos<SUP>+</SUP> cells were comparable with the sham group at 56 days after MI. Therefore, MI may induce c-Fos immunoreactivity in PVNH and PVNT, this increase of c-Fos expression levels may be associated with the stress that occurs in the brain following MI.</P>

Noradrenergic Modulation of Spontaneous Inhibitory Postsynaptic Currents in the Hypothalamic Paraventricular Nucleus

Lee, Long-Hwa,Chong, Won-Ee,Lee, Ki-Ho,Park, Jin-Bong,Ryu, Pan-Dong The Korean Society of Pharmacology 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.2

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE $(30{\sim}100{\mu}M)$ reversibly decreased sIPSC frequency to $41{\pm}7%$ of the baseline value $(4.4{\pm}0.8\;Hz,\;p<0.001).$ This effect was blocked by yohimbine $(2{\sim}20{\mu}M),$ an ${\alpha}_2-adrenoceptor$ antagonist and mimicked by clonidine $(50{\mu}M),$ an ${\alpha}_2-adrenoceptor$ agonist. In contrast, NE increased sIPSC frequency to $248{\pm}32%$ of the control $(3.06{\pm}0.37\;Hz,\;p<0.001)$ in 31 of 54 type II neurons, but decreased the frequency to $41{\pm}7$ of the control $(5.5{\pm}1.3\;Hz)$ in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 $M{\Omega},$ p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via ${\alpha}_2-adrenoceptor,$ however, either increases in about 60% or decreases in 40% of type II neurons.