• BMB Reports
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• v.54 no.12
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• pp.620-625
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• 2021

Microglia are known to be activated in the hypothalamic paraventricular nucleus (PVN) of rats with cardiovascular diseases. However, the exact role of microglial activation in the plasticity of presympathetic PVN neurons associated with the modulation of sympathetic outflow remains poorly investigated. In this study, we analyzed the direct link between microglial activation and spontaneous firing rate along with the underlying synaptic mechanisms in PVN neurons projecting to the rostral ventrolateral medulla (RVLM). Systemic injection of LPS induced microglial activation in the PVN, increased the frequency of spontaneous firing activity of PVN-RVLM neurons, reduced GABAergic inputs into these neurons, and increased plasma NE levels and heart rate. Systemic minocycline injection blocked all the observed LPS-induced effects. Our results indicate that LPS increases the firing rate and decreases GABAergic transmission in PVN-RVLM neurons associated with sympathetic outflow and the alteration is largely attributed to the activation of microglia. Our findings provide some insights into the role of microglial activation in regulating the activity of PVN-RVLM neurons associated with modulation of sympathetic outflow in cardiovascular diseases.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.59-70
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• 2008

Objectives: Investigation of the antidepressant effects of Citri Reticulatae Viride Pericarpium(CR) Methods: In order to investigate the antidepressant effects of Citri Reticulatae Viride Pericarpium(CR), we performed the forced swimming test. Also the expression of CRF, HSP70 and c-fos was measured with immunohistochemical method at PVN. Results: 1. The duration of immobility in the forced swimming test was significantly decreased in the CR 100mg/kg, 400mg/kg groups. 2. In the Control group, CRF expression was significantly increased in the PVN. Also, these CRF increase were significantly reduced in the CR 100mg/kg and 400mg/kg treated group. 3. HSP70 expression was significantly decreased at PVN in the CR 100mg/kg and 400mg/kg treated group. 4. C-fos expression was significantly decreased at PVN in the CR 100mg/kg and 400mg/kg treated group. Conclusions: According to the results, it can be considered that Citri Reticulatae Viride Pericarpium has antidepressant effect.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.1
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• pp.41-46
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• 2001

To investigate the mutual relationship between angiotensin II (Ang II) and nitric oxide (NO) in paraventricular nucleus (PVN), Ang II receptor type Ia $(AT_{1A}),$ type Ib $(AT_{1B}),$ endothelial constitutive nitric oxide synthase (ecNOS), and neuronal constitutive nitric oxide synthase (ncNOS) mRNA levels of rat PVN were measured after unilateral carotid artery ligation. $AT_{1A}$ and $AT_{1B}$ mRNA levels were markedly elevated 6 hrs after unilateral carotid artery ligation. Losartan injection $(10\;{\mu}g/0.3\;{\mu}l)$ into the PVN augmented of the increment of $AT_{1A}$ and $AT_{1B}$ mRNAs It also increased ecNOS gene expression. In addition, $AT_{1B}$ mRNA levels increased after N-nitro-L-arginine methyl ester (L-NAME) injection $(50\;{\mu}g/0.3\;{\mu}l)$ into the PVN. These results suggest that Ang II and NO in the rat PVN may interplay, at least in part, through regulation of gene expression of ecNOS and $AT_{1B},$ respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.5
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• pp.333-337
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• 2012

Gene expression of neuronal nitric oxide synthase (nNOS) changes in the hypothalamic paraventricular nucleus (PVN) depending on feeding conditions, which is decreased during food deprivation and restored by refeeding, and phosphorylated cAMP response element binding protein (pCREB) was suggested to play a role in its regulation. This study was conducted to examine if the fasting-induced down-regulation of the PVN-nNOS expression is restored by activation of cAMP-dependent protein kinase A (cAMP/PKA) pathway. Freely moving rats received intracerebroventricular (icv) injection of cAMP/PKA activator Sp-cAMP (40 nmol) or vehicle (sterilized saline) following 48 h of food deprivation. One hour after drug injections, rats were transcardially perfused with 4% paraformaldehyde, and the PVN tissues were processed for nNOS or pCREB immunohistochemistry. Sp-cAMP significantly increased not only nNOS but also pCREB immunoreactivities in the PVN of food deprived rats. Fastinginduced down-regulation of the PVN-nNOS was restored by 1 h after the icv Sp-cAMP. Results suggest that cAMP/PKA pathway may mediate the regulation of the PVN-nNOS expression depending on different feeding conditions.

• The Journal of Internal Korean Medicine
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• v.34 no.2
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• pp.113-121
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• 2013

Objectives : This study aimed to find out whether acupuncture at various acupoints shows any effects on appetite by regulating neurotransmitters in the hypothalamus through the expression of NPY and LR in the PVN via immunohistochemistry. Methods : Male Sprague-Dawley rats were divided into eight groups of five mice each. The rats in the acupuncture groups were treated with acupuncture at respective acupoints, twice per a day for 3 days. The animals were sacrificed 72 h after commencement of the experiment, the brains being dissected into serial coronal sections. Expressions of neuropeptide Y and leptin receptor in the hypothalamus were assessed by immunohistochemistry. Results : NPY expression in the PVN was enhanced and LR expression in the PVN was decreased by food deprivation. NPY immunoreactivity in the PVN of the food-derived rats was decreased by acupuncture at the auricular acupoint, Zusanli-acupoint, a and non-acupoint. However, acupuncture at the auricular acupoint showed most potent suppressing effect on NPY expression in the PVN of food-deprived rats. LR expression in the PVN decreased following food deprivation, and auricular acupuncture increased LR expression in the PVN of food-deprived rats. In normal conditions (fed state), LR expression in the PVN was not changed by acupuncture treatment at several sites. Conclusions : From this study, we have shown that acupuncture at the auricular acupoint exerts the most potent appetite suppressing effect on the food restriction state.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Applied Chemistry for Engineering
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• v.5 no.3
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• pp.537-546
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• 1994

The physical characteristics of polymer modified asphalt depend on many parameters, such as, the polymer nature, polymer content and the asphalt properties. The objective of this study is to investigate the temperature susceptibility of polymer modified asphalt. The asphalts employed in this study were two different grades : a soft(200/300) grade and a hard(85/100) grade. And chlorinated polyethylene of two different characteristics were used : plastomer(Tyrin 2552) and elastomer(Tyrin CM0730). Temperature susceptibility of asphalt is a fundamental feature for characterizing asphalt and modified asphalt. It can be quantified by the penetration index(PI) and pen-vis number(PVN). These indices were obtained from the measurements of penetration and viscosity of the asphalt samples. For both of asphalts, the addition of the polymers increases the value of PI and PVN. Plastomer modified asphalt shows higher value of PI and PVN than elastomer modified asphalt. Soft grade shows more temperature susceptibility than hard grade at elevated temperatures.

• Korean Journal of Acupuncture
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• v.24 no.4
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• pp.221-231
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• 2007

목 적 : 본 연구의 목적은 시상하부에서 침처치에 대한 nitric oxide synthase (NOS)발현을 nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)를 이용한 조직화학 염색법으로 관찰하였다. 실험방법 : 동물은 Balb/c (wild type) 와 Stat 4 knockout (KO) 생쥐를 사용하였다. 염증유도는 1% carrageenan 용액 (20ul/마리)을 발 뒤꿈치 표피에 주사하였고, 침 처치는 족삼리 (ST36)에 시침하였다. 침 처치 후 5시간까지 부종율을 부종측정기로 측정하였으며, 마지막으로 부종을 측정한 후 동물을 희생하여 뇌를 적출하여 고정하였다. 침에 대한 효과를 확인하기 위하여 NADPH-d 반응의 조직염색을 실시하였다. 염증유도와 그룹간의 유의성 검증은 one-way ANOVA를 사용하였다. 결 과 : 대조군인 Balb/c와 실험군인 stat4 KO 생쥐를 carrageenan으로 염증을 유도시에 대조군은 90%이상 유도된 반면, Stat4 KO 그룹은 50% 정도의 염증만이 유도되었다. 염증을 유도한 생쥐의 족삼리에 침 처치시 대조군은 1시간에서 약 40%정도 감소하였고 (P<0.05), Stat4 KO 실험군은 유의한 염증 감소율을 보이지 않았다. 시상하부의 lateral hypothalamic area (LHA)와 paraventricular nucleus (PVN)부위의 침에 대한 효과를 NADPH-d 에 양성으로 반응하는 세포수로 비교하여 다음과 같은 결과를 얻었다. (1) 대조군에서 염증 유도시 시상하부의 PVN는 NADPH-d 양성세포수가 감소하였고, LHA에서는 증가하였다. (2) 염증을 유도한 대조군에 침을 처치시 PVN은 세포수가 증가하였고, LHA에서는 감소하는 경향을 보였다. (3) 염증을 유도한 Stat4 KO 군에서는 시상하부의 PVN과 LHA부위 모두에서 NADPH-d 양성세포수가 감소하였고, 염증유도그룹에 침을 처치시 PVN과 LHA부위 모두에서 세포수가 증가함을 관찰 할 수 있었다. (4) 대조군과 실험군 모두에 salicylic acid로 비교하였더니 염증유도 효과 및 NADPH-d 세포 수에서 침 처치와 비슷한 결과를 나타내었다. 결 론 : 침은 염증을 유도한 생쥐에서 염증 감소에 유의한 효과가 있다. 염증을 유도한 Balb/c 와 Stat4 KO 생쥐에 침을 처치 시 시상하부의 NADPH-d 발현이 LHA부위와 PVN에서 서로 다르게 나타나는 것으로 나타난다. 이러한 현상은 침 효과가 시상하부의 위치에 대한 작용이 다르기 때문이라고 생각된다.

• Journal of Oriental Neuropsychiatry
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• v.14 no.1
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• pp.1-16
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• 2003

Objective : This study was designed to assess the protective effects of Hwangryeonhaedoktang on the animal model of depression, induced by chronic mild stress(CMS). Method : Male Sprague-Dawley rats were used for this experiment. The subjects were divided into 3 groups ( 1. CMS-drug: Hwangryeonhaedoktang administered during CMS treatment, 2. CMS-vehicle: water administered, 3. normal ). After 4 weeks of CMS treatment, they were executed forced swimming test(FST), open field test and c-Fos in paraventricular nucleus(PVN) were measured. Result : 1. In FST, immobility behavior decreased significantly in CMS-drug group. 2. There was no difference in the open field test between 3 groups 3. c-Fos expressed cell bodies in PVN were significantly less in CMS-drug than in CMS-vehicle group. Conclusion : These results suggest that Hwangryeonhaedoktang may have protective antidepressant effects in CMS model rats. And these effects could be explained by the elevated stress-copying behaviors which are related with PVN of hypothalamus.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.71-80
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• 2002

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.