• BMB Reports
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• 제54권12호
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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.

• Journal of Microbiology and Biotechnology
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• 제18권12호
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• pp.1990-1996
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• 2008

Astaxanthin has shown antioxidant, antitumor, and anti-inflammatory activities; however, its molecular action and mechanism in the nervous system have yet to be elucidated. We examined the in vitro effects of astaxanthin on the production of nitric oxide (NO), as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Astaxanthin inhibited the expression or formation of nitric oxide (NO), iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Astaxanthin also suppressed the protein levels of iNOS and COX-2 in LPS-stimulated BV2 microglial cells. These results suggest that astaxanthin, probably due to its antioxidant activity, inhibits the production of inflammatory mediators by blocking iNOS and COX-2 activation or by the suppression of iNOS and COX-2 degradation.

• Advances in Traditional Medicine
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• 제5권3호
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• pp.216-230
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• 2005

Although the field of study in immune enhancing compounds is relatively new, natural products from plants represent a rich and promising source of novel molecules with immunomodulating properties, Microglial cells, the main immune effector cells of the brain, usually display a ramified morphology and low expression levels of immunologically relevant antigens such as MHC class I and class II. Since any compound which participates in activation of phagocytic cells contributes to the production of potentially toxic factors, the search for convenient in vitro test-systems and study of mechanisms of action of these agents are of great interest. Human blood polymorphonuclear (PMN) cells and primary microglial cells isolated from Sprague-Dawley rats were used as cellular screening tests for study of phagocytosis-stimulating action of immunomodulating agents. Numbers of phagocytic activity were evaluated by the phagocyte ingestion of yeast cells and NO-synthase activity, nitrite production, and nitroblue tetrazolium test were determined after phagocyte stimulation. It was possible to demonstrate that indexes of phagocytic activity can be used as quantitative indicators for measurement immunomodulating activity. As a positive control, Zymosan A-induced phagocytosis in both PMN cells and primary microglial cells was used. $IFN-{\gamma}$ (0.1 -1 U/ml) stimulated phagocytosis in PMN cells 1.2 times after 2 - 3 h incubation, although at higher concentrations (10 - 100 U/ml) it strongly inhibited phagocytosis. In a similar way, at higher concentrations, $IFN-{\gamma}$ (100 - 500 U/ml) suppressed phagocytosis in zymosan-A stimulated microglial cells. When Polypodium leucotomus, cambricum and vulgare extracts were tested alone, increased levels of phagocytosis were observed in PMN. In addition, microglial cells showed both increased phagocytosis and MHC class-II antigen expressions. Surprisingly, when PMN and microglia were treated with a combination of Polypodium and $IFN-{\gamma}$, phagocytosis was not inhibited. We did not find changes in NO-synthase activity and nitrite production in both microglia and PMN cells activated by different immunomodulating agents. These results indicate that primary microglial cell cultures as well as human PMN cells can provide reproducible quantitative results in screening phagocytic activity of different immunoactive compounds. Furthermore, both inhibitory or activation mechanisms might be studied using these in vitro experimental approaches.

• Korean Journal of Acupuncture
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• 제41권2호
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• pp.33-42
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• 2024

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

• 동의신경정신과학회지
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• 제19권2호
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• pp.65-75
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• 2008

Objective : This experiment was designed to investigate the effect of the KBHT and PMCMT extract on protecting microglia and inhibiting acetylcholinesterase and oxidants. Method : The effects of the KBHT and PMCMT extract on cell death of BV2 microglial cell line treated by ${\gamma}$ ; expression of NO, ROS in BV2 microglial cell line treated by lipopolysaccharide(LPS) ; AChE activity in PC-12 cell treated by NGF were investigated, respectively. Result : The KBHT and PMCMT extract significantly increased cell viability in BV2 microglial cell line treated with ${\gamma}$. The KBHT and PMCMT extract suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. The KBHT and PMCMT extract groups also showed inhibition of AChE activity in PC-12 cell line. Conclusion : According to the above result, it is suggested that the KBHT and PMCMT extract might be usefully applied for prevention and treatment of Alzheimer' s disease.

• 동의생리병리학회지
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• 제22권5호
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• pp.1276-1282
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• 2008

This experiment was designed to investigate the effect of the ODTCMT and DDTCMT extract on protecting microglia and inhibiting acetylcholinesterase and oxidants. The effects of the ODTCMT and DDTCMT extract on cell death of BV2 microglial cell line treated by $IFN-{\gamma}$ ; expression of NO, ROS in BV2 microglial cell line treated by lipopolysaccharide (LPS) ; AChE activity in PC-12 cell treated by NGF were investigated, respectively. The ODTCMT and DDTCMT extract significantly increased cell viability in BV2 microglial cell line treated with $IFN-\nu$. The ODTCMT and DDTCMT extract suppressed the NO and RDS production in BV2 microglial cell line treated by LPS. The ODTCMT and DDTCMT extract groups also showed inhibition of AChE activity in PC-12 cell line. According to the above result, it is suggested that the ODTCMT and DDTCMT extract might be usefully applied for prevention and treatment of Alzheimer's disease. OnDam-TanghapChongMyoung-Tang (ODTCMT), DoDam-TanghapChongMyoung-Tang (DDTCMT), Microglia, acetylcholinesterase, ROS

• 동의생리병리학회지
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• 제22권1호
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• pp.120-125
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• 2008

This experiment was designed to investigate the effect of the CBD and SJT extract on protecting microglia and inhibiting acetylcholinesterase and oxidants. The effects of the CBD and SJT extract on cell death of BV2 microglial cell line treated by $IFN-{\gamma}$ ; expression of NO, ROS in BV2 microglial cell line treated by lipopolysaccharide(LPS) ; AChE activity in PC-12 cell treated by NGF were investigated, respectively. The CBD and SJT extract significantly increased cell viability in BV2 microglial cell line treated with $IFN-{\gamma}$. The CBD and SJT extract suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. The CBD and SJT extract groups also showed inhibition of AChE activity in PC-12 cell line. According to the above result, it is suggested that the CBD and SJT extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• 대한의생명과학회지
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• 제24권4호
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• pp.305-310
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• 2018

Microglia are emerging as critical regulators of innate immune responses in AD and other neurodegenerative disorders, highlighting the importance of understanding their molecular and cellular mechanisms. We attempted to determine the role of crosstalk signaling between $IFN-{\gamma}$ and $TGF-{\beta}$ in $A{\beta}$ clearance by microglia cells. We used in vitro and in vivo mouse models that recapitulated acute and chronic aspects of microglial responses to $A{\beta}$ peptides. We showed that crosstalk signaling between $TGF-{\beta}$ and Smad2 was an important mediator of neuro-inflammation. These findings suggest that microglial $TGF-{\beta}$ activity enhances the pathological progression to AD. As $TGF-{\beta}$ displays broad regulatory effects on beneficial microglial functions, the activation of inflammatory crosstalk signaling between $TGF-{\beta}$ and Smad2 may be a promising strategy to restore microglial functions, halt the progression of $A{\beta}$-driven pathology, and prevent AD development.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.295-302
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• 2021

Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.

• The Korean Journal of Physiology and Pharmacology
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• 제11권1호
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• pp.9-13
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• 2007

Antioxidant properties have been proposed as a mechanism for the putative anti-inflammatory effects of phenolic compounds. To reveal the relationship between antioxidant activity and anti-inflammatory effects of various antioxidants, we measured 1, 1-diphenyl-2-picryhydrazyl(DPPH)-reducing activity and examined the inhibitory effects on LPS-induced inflammation-related gene expression in the BV2 microglial cell line. Lipopolysaccharide(LPS)(0.2 ${\mu}g/ml$) was used with or without antioxidants to treat cells, and the regulation of iNOS and cytokine gene expression was monitored using an RNase protection assay(RPA). Although, all tested antioxidants had similar DPPH-reducing activity and inhibited nitrite production, but the curcuminoid antioxidants(ferulic acid, caffeic acid, and curcumin) inhibited LPS-induced gene expression(iNOS, $TNF-\alpha,\;IL-1{\beta}$, IL-6, and IL-1 Ra) in a concentration-dependent manner. Other tested antioxidants did not exhibit the same effects; N-acetylcysteine(NAC) only began to suppress $IL-1{\beta}$ gene expression just below the concentration at which cytotoxicity occurred. Moreover, the antioxidant potency of curcuminoids appeared to have no correlation with anti-inflammatory potency. Only curcumin could inhibit LPS-induced microglial activation at a micromolar level. These data suggest that curcumin may be a safe antioxidant possessing anti-inflammatory activity.