• International Journal of Oral Biology
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• 제39권1호
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• pp.49-56
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• 2014

이상의 실험결과들을 요약하면, CFA를 안면영역 피하로 주입하여 발생한 염증성 통증 행위반응은 P2X 수용체의 억제제의 투여로 감소할 수 있었다. 특히 $P2X_7$ 수용체 억제제를 투여하면 진통작용 뿐 아니라 활성화된 신경아교세포 발현을 억제하였다. 이러한 실험 결과는 $P2X_7$ 수용체가 신경아교세포에 영향을 미쳐 안면에서 발생하는 만성 염증성 통증의 발생과 유지에 관여하고 있다는 것을 보여준다. 따라서 중추신경계의 신경아교세포를 조절할 수 있는 중추성 $P2X_7$ 수용체 작용기전은 임상에서 만성 염증성 통증을 보다 효과적으로 치료할 수 있는 새로운 방법을 제시해 줄 수 있다고 생각된다.

• 동의신경정신과학회지
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• 제17권2호
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• pp.91-122
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• 2006

Objective : This research investigates the effect of the Jangwon-Dan,(JWD) on Alzheimer's disease. Method : The effects of the JWN extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA, the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA, (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : 1. The JWN extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The JWN extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The JWN extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the JWN extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The JWN extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and CD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The JWN extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion : These results suggest that the JWN extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the JWN extract for Alzheimer's disease is suggested for future research.

• 동의신경정신과학회지
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• 제15권2호
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• pp.119-139
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• 2004

This research investigates the effect of the Hibiscus syriacus(HSS) on Alzheimer's disease. Specifically, the effects of the HSS extract on (1) $IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and reactive oxygen species(ROS); (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized below ; 1. The HSS extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-l cells treated with LPS. 2. The HSS extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The HSS extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the HSS extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The HSS extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, $IL-1{\beta}$ and $TNF-{\alpha}$ mRNA, CD68/GFAP, ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The HSS extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the HSS extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the HSS extract for Alzheimer's disease is suggested for future research.

• 대한수의학회지
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• 제51권3호
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• pp.217-225
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• 2011

Glatiramer acetate (GA; Copaxone) has been shown to be effective in preventing and suppressing experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). It has been recently shown that GA-reactive T cells migrate through the blood-brain barrier, accumulate in the central nervous system (CNS), secrete antiinflammatory cytokines and suppress production of proinflammatory cytokines of EAE and MS. Development of EAE requires coordinated expression of a number of genes involved in the activation and effector functions of inflammatory cells. Activation of inflammatory cells is regulated at the transcriptional level by several families of transcription factors. One of these is the nuclear factor kappa B ($NF{\kappa}B$) family which is present in a variety of cell types and involved in the activation of immune-relative genes during inflammatory process. Since it is highly activated at site of inflammation, $NF{\kappa}B$ activation is also implicated in the pathogenesis of EAE. In this study, we examined whether the inhibition of $NF{\kappa}B$ activation induced by GA can have suppressive therapeutic effects in EAE mice. We observed the expression of $NF{\kappa}B$ and phospho-$I{\kappa}B$ proteins increased in GA-treated EAE mice compared to EAE control groups. The immunoreactivity in inflammatory cells and glial cells of $NF{\kappa}B$ and phospho-$I{\kappa}B$ significantly decreased at the GA-treated EAE mice. These results suggest that treatment of GA in EAE inhibits the activation of $NF{\kappa}B$ and phophorylation of $I{\kappa}B$ in the CNS. Subsequently, the inhibition of $NF{\kappa}B$ activation and $I{\kappa}B$ phosphorylation leads to the anti-inflammatory effects thereby to reduce the progression and severity of EAE.

• Applied Microscopy
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• 제28권4호
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• pp.425-434
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• 1998

This study was designed to investigate the microglial reactions to the neurodegenerative changes in the cat retina. All experiments were performed using adult cats of both sex, weighing $2,500g\sim3,500g$. 5,7-DHT $(100{\mu}g)$ dissolved in 0.1% ascorbic acid was injected into the vitreous body. All injections were performed in one-side eye; the other side served as the control, which was injected only with 0.1% ascorbic acid. Cats were sacrificed at 1, 3, 7, 14 and 21 days after intravitreal injection of 5,7-DHT For light microscopy, retinae were fixed with 4% paraformaldehyde and processed using NDPase histochemistry. Same retinae were fixed with 1% para(formaldehyde-2.5% glutaraldehyde and processed for electron microscopy. NDPase-positive microglial cells were mainly distributed in the inner plexiform layer of the retina, and characterized by a small somata with a few slender processes, which were also extended in the ganglion cell layer (GCL) and inner nuclear layer (INL). The intensity of the microglia stained for NDPase was abruptly increased at 7 day as compared with that of the control, and thereafter continuously sustained until 21 day, the last experimental group in this study. Under the electron microscopical observation, microglial cells in the control group exhibited elongate nucleus with perinuclear chromatin condensation, and the perikaryon was scanty. However, a few hypertrophic glial cells were frequently found at 3 days after the drug injection. By 7 day, most microglial cells directed toward the degenerated neurons in the GCL, and the number of microglial cells was slightly increased as compared with the former group. At the 14 day, most microglial cells wrapped the degenerated cells in the GCL, and a few cells showed phagocytotic features. By 21 day, most microglial cells were engaged in phagocytotic activity, and their cytoplasm was filled with the phagorytosed material. Based on the results, 5,7-DHT may act as a specific neurotoxin to the cat retina, and microglial reactions to the neuronal death are already induced in early experimental stage. These results indicate that the microglial cells in the cat retina show characteristic features as a protective effect of neural tissue.

• 동의신경정신과학회지
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• 제16권1호
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• pp.97-117
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• 2005

This research investigates the effect of the Chaenomelis fructus(CMF) on Alzheimer's disease. Specifically, the effects of the CMF extract on (1) >$IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior of AD mice with ${\beta}A$; (5) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and ROS; (6) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized as follows; 1. The CMF extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The CMF extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The CMF extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. A significant inhibitory effect on the memory deficit was shown on the CMF extract group of the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 5. The CMF extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ protein, mRNA, $TNF-{\alpha}$ mRNA, CD68/GFAP, and ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The CMF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer’s disease induced by ${\beta}A$. These results suggest that the CMF extract may be effective for the treatment of Alzheimer’s disease. Investigation into the clinical use of the CMF extract for Alzheimer's disease is suggested for future research.

• Journal of Neurogastroenterology and Motility
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• 제26권1호
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• pp.106-116
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• 2020

Background/Aims Emerging evidence shows that the mechanism of irritable bowel syndrome (IBS) is associated with neurotrophic factors and tight junction proteins (TJPs). It is known that there are sex differences in the pathophysiology of IBS. The aim of the present study is to determine expression levels of neurotrophic factors, TJPs, and cytokines according to IBS subtype and sex. Methods From 59 IBS (33 IBS-constipation, 21 IBS-diarrhea, and 5 IBS-mixed) and 36 control patients, colonic mucosa mRNA expression levels of transient receptor potential vanilloid-1 (TRPV1), nerve growth factor (NGF), glial cell-derived neurotrophic factor (GDNF), and various TJPs were assessed by real-time polymerase chain reaction. Western blot was performed to determine levels of zonular occludens-1 (ZO-1). Serum levels of cytokines were measured by enzyme-linked immunosorbent assay. Results TRPV1, GDNF, and NGF mRNA levels were significantly increased in those with IBS-constipation compared to those in controls (all P < 0.05). However, they showed no significant difference between those with IBS-diarrhea and controls. Expression level of TRPV1 correlated with that of GDNF (r = 0.741, P < 0.001) and NGF (r = 0.935, P < 0.001). ZO-1 RNA expression levels were lower (P = 0.021) in female IBS-diarrhea than those in controls, although they showed no significant differences between male IBS-diarrhea and controls. Serum IL-1β levels in female IBS were significantly higher than those of male IBS, especially in IBS-constipation (P < 0.001). Conclusion Our results suggest that neurotrophic factors and IL-1β are closely related to IBS-constipation and that decrease of ZO-1 is an important factor in female with IBS-diarrhea.

• 대한본초학회지
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• 제36권6호
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• pp.1-8
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• 2021

Objectives : Atractylodis rhizoma Alba has been traditionally used as a medicinal resource that is used for enhancing Qi (氣) in traditional medicine in Korea, China, and Japan. This study investigated the protective effects of Atractylodis rhizoma Alba extract (ARE) against trimethyltin (TMT), a neurotoxin that causes selective hippocampal injury, using both in vitro and in vivo models. Methods : We investigated the effects of ARE on TMT- (5mM) induced cytotoxicity in primary cultures of mouse hippocampal cells (7 days in vitro ) and on hippocampal injury in C57BL/6 mice injected with TMT (2.6 mg/kg). Results : We observed that ARE treatment (0 - 50 ㎍/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, based on results of lactate dehydrogenase and 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that orally administered ARE (5 mg/kg; between -6 and 0 days before TMT injection) significantly attenuated seizures in adult mice. Furthermore, quantitative analysis of allograft inflammatory factor-1 (Iba-1)- and glial fibrillary acidic protein (GFAP)- positive cells showed significantly reduced levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus of mice treated with ARE prior to TMT injection. These findings indicate the significant protective effects of ARE against the TMT-induced massive activation of microglia and astrocytes in the hippocampus. Conclusions : We conclude that ARE minimizes the detrimental effects of TMT-induced hippocampal neurotoxicity, both in vitro and in vivo . Our findings may serve as useful guidelines to support ARE administration as a promising pharmacotherapeutic approach to hippocampal degeneration.

• 생명과학회지
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• 제31권12호
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• pp.1120-1127
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• 2021

우울증은 높은 유병률과 자살률 증가로 인해 사회적 기능에 부정적인 영향을 미치며, 경제적 부담 또한 높은 질환이다. 우울증은 신경염증, 시냅스 기능장애, 인지 결손과 같은 뇌에서 다양한 현상과 관련이 있다. 임상에서 사용되는 항우울제들은 치료효과가 낮아 빠른 효능을 보이는 항우울제 개발이 시급하다. 현재까지 우울증과 관련된 다양한 유전자, 단백질, 그리고 신호전달계에 대한 많은 연구가 수행되었지만, 우울증의 발생기전은 명확하게 밝혀지지 않았다. Sirtuin 1은 nicotinamide-adenine dinucleotid- (NAD⁺-) dependent histone deacetylases로써 세포 분화, 세포 사멸, 발생, 자가소화작용, 암 대사에 관여하는 것으로 알려져 있다. 최근의 유전연구들은 Sirtuin 1이 우울증의 잠재적 타겟 유전자라고 제안하고 있다. 또한 전임상 연구에서는 Sirtuin 1의 신호전달기전이 우울행동에 영향을 미친다고 보고 하였다. 본 종설에서는 우울증과 Sirtuin 1에 대한 최신 지식을 제시하였다. 소교세포의 활성, 일주기 생체 리듬, 신경세포 생성, 및 인지기능의 조절에 관여하는 Sirtuin 1이 우울증에 미치는 다양한 영향을 설명하였다. 아울러 Sirtuin 1이 우울증 핵심 기전중의 하나인 신경가소성의 손상에 미치는 영향과 그 기전에 대해서 논의하였다.

• 대한본초학회지
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• 제29권3호
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• pp.27-33
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• 2014

Objectives : The aim of this study was to investigate the protective effect of extract of Thuja orientalis leaves (TOFE) against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by inhibition of inflammation in in vitro and in vivo models of Parkinson's disease (PD). Methods : We evaluated the effect of TOFE against lipopolysaccharide (LPS)/1-methyl-4-phenylpyridinium ($MPP^+$) toxicity using nitric oxide (NO) assay, inducible NO synthase and cyclooxygenase 2 western blot, tyrosine hydroxylase and microglia activation immunohistochemistry (IHC) in BV2 cell, primary rat mesencephalic neurons, or C57BL/6 mice. We also evaluated the effect of TOFE in mice PD model induced by MPTP. C57BL/6 mice were treated with TOFE 50 mg/kg for 5 days and were injected intraperitoneally with four administrations of MPTP on the last day. We conducted behavioral tests and IHC analysis to see how TOFE affect MPTP-induced neuronal loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) and striatum (ST) of mice. To assess the anti-inflammation effects, we carried out glial fibrillary acidic protein and macrophage-1 antigen integrin alpha M in IHC in SNpc and ST of mice. Results : In an in vitro system, TOFE decreasesd NO generations in BV2 cells. TOFE protected dopaminergic cells against LPS or $MPP^+$-induced toxicity in primary mesencephalic dopaminergic neurons. In vivo system, TOFE at 50 mg/kg treated group showed improved motor deteriorations than the MPTP only treated group and TOFE significantly protected striatal dopaminergic damage from MPTP-induced neurotoxicity in mice. Moreover, TOFE inhibited activation of astrocyte and microglia in SNpc and ST of the mice. Conclusions : We concluded that TOFE showed anti-parkinsonian effect by protection of dopaminergic neurons against MPTP toxicity through anti-inflammatory actions.