• IMMUNE NETWORK
• /
• v.14 no.1
• /
• pp.54-65
• /
• 2014

Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, with the ability to differentiate into different cell types. Additionally, the immunomodulatory activity of MSCs can downregulate inflammatory responses. The use of MSCs to repair injured tissues and treat inflammation, including in neuroimmune diseases, has been extensively explored. Although MSCs have emerged as a promising resource for the treatment of neuroimmune diseases, attempts to define the molecular properties of MSCs have been limited by the heterogeneity of MSC populations. We recently developed a new method, the subfractionation culturing method, to isolate homogeneous human clonal MSCs (hcMSCs). The hcMSCs were able to differentiate into fat, cartilage, bone, neuroglia, and liver cell types. In this study, to better understand the properties of neurally differentiated MSCs, gene expression in highly homogeneous hcMSCs was analyzed. Neural differentiation of hcMSCs was induced for 14 days. Thereafter, RNA and genomic DNA was isolated and subjected to microarray analysis and DNA methylation array analysis, respectively. We correlated the transcriptome of hcMSCs during neural differentiation with the DNA methylation status. Here, we describe and discuss the gene expression profile of neurally differentiated hcMSCs. These findings will expand our understanding of the molecular properties of MSCs and contribute to the development of cell therapy for neuroimmune diseases.

• Journal of Oriental Neuropsychiatry
• /
• v.9 no.1
• /
• pp.73-82
• /
• 1998

Substantial evidence has accumulated that Alzheimer's disease is associated with a local inflammatory reaction in senile plaques which may be immunemediated, and includes extensive Brain Neuroglial invasion, lymphocytic infiltration, cytokine deposition. Tumor necrosis factor a (TNF-a) is a cytokine which plays an important immunoenhancing role in the local acute and chronic inflammatory response in response to a variety of stimuli. The neuropeptide, substance P, can stimulate secretion of TNF-a from Brain Neuroglial cells. Neuroglia have substance P receptors in the central nervous system. WQ investigated whether RADIX ASPARAGI inhibits secretion of TNF-a from primary cultures of Brain Neuroglial cells containing both astrocyte (∼90%) and microglia (∼10%). RADIX ASPARAGI dose-dependently inhibited the TNF-a secretion induced by substance P plus lipopolysaccharide (LPS). In cultures enriched for micoglia (>95% pure). LPS stimulated the secretion of TNF-a but substance P caused no enhancement. Because there was no synergism between substance P and LPS in the microglial cultures it is resonable to substance P madiated enhancement of TNF-a secretion. IL-1 is a modulator of TNF-a secretion in the immune system. Also IL-1 has been shown to elevate TNF- a secretion from LPS-stimulated Brain Neuroglial cells while having no effect on Brain Neuroglial cells in the absence of LPS. We therfore investigated whether IL-1 mediates the RADIX ASPARAGI inhibition of TNF-a secretion form primary Brain Neuroglial cells. Treatment of RADIX ASPARAGI to mixed cultures stimulated with both substance P and LPS decreased TNF-a secretion to the level observed with LPS alone. These results indicate that RADIX ASPARAGI possess strong antiinflammatory activity in the cental nervous system by inhibition of inflammatory cytokines secretion from Brain Neuroglial cells.

• The Journal of the Korea Contents Association
• /
• v.16 no.4
• /
• pp.36-44
• /
• 2016

This article serves as a guideline to the policy on Korea brain science program. Given limited resources within Korea, setting priorities in brain science topics is important in science policy. In this study, we determined the priorities of important brain science topics based on the frontier properties, innovativeness, and prospective outcome. Firstly, the significant topics were chosen after the interview with the top nationwide brain scientists, which were neuroglia, brain precision medicine, neuromorphic engineering, neuroepigenetics, and brain oscillation. Secondly, the analytic hierarchy process (AHP) survey were conducted to prioritize and assign the important weight for not only the criteria but also the research topics in pair choice evaluation. In regards to the importance among the criteria, prospects of the topic was determined to be the top criterion to ranked criterion to consider in the government investment. The priority of the research topics was determined by the order for the project to be considered in national science policy in a comparative way.

• Journal of Korean Medicine for Obesity Research
• /
• v.20 no.1
• /
• pp.10-19
• /
• 2020

Objectives: Oxidative stress-mediated neuroinflammation has been supposed as a crucial factor that contributes to the pathogenesis of many neurodegenerative diseases. In this study, we aimed to investigate the protective activity against oxidative stress and neuroinflammation of protocatechuic acid (PA), active phenolic compound from Momordica Charantia. Methods: Protective activity of PA from oxidative stress was performed under in vitro conditions. Our study investigated the protective mechanism of PA from neuroinflammation in cellular system using C6 glial cell. To investigate the improvement the effects on oxidative stress and neuroinflammation, we induced oxidative stress by H₂O₂ (100 μM) stimulation and induced neuroinflammation by treatment with lipopolysaccharide (LPS) (1 ㎍/mL) and interferon-gamma (IFN-γ) (10 ng/mL) in C6 glial cells. Results: PA showed strong radical scavenging effect against 1,1-dipenyl-2-picrylhydrazyl, hydroxy radical (·OH) and nitric oxide (NO). Under oxidative stress treated by H₂O₂, the result showed the increased mRNA expressions of oxidative stress markers such as nuclear factor-kappaB (NF-κB), cyclooxygenase (COX-2) and inducible nitric oxide (iNOS). However, the treatment of PA led to reduced mRNA expressions of NF-κB, COX-2 and iNOS. Moreover, PA attenuated the production of interleukin-6 and scavenged NO generated by both endotoxin LPS and IFN-γ together. Furthermore, it also reduced LPS and IFN-γ-induced mRNA expressions of iNOS and COX-2. Conclusions: In conclusion, our results collectively suggest that PA, phenolic compound of Momordica Charantia, could be a safe anti-oxidant and a promising anti-neuroinflammatory molecule for neurodegenerative diseases.

• Nutrition Research and Practice
• /
• v.13 no.4
• /
• pp.279-285
• /
• 2019

BACKGROUND/OBJECTIVES: Excessive production of reactive oxygen species (ROS) such as hydroxyl (${\cdot}OH$), nitric oxide (NO), and hydrogen peroxide ($H_2O_2$) is reported to induce oxidative stress. ROS generated by oxidative stress can potentially damage glial cells in the nervous system. Cordyceps militaris (CM), a kind of natural herb widely found in East Asia. In this study, we investigated the free radical scavenging activity of the CM extract and its neuroprotective effects in $H_2O_2$-induced C6 glial cells. MATERIALS/METHODS: The ethanol extract of CM ($100-1,000{\mu}g/mL$) was used to measure DPPH, ${\cdot}OH$, and NO radical scavenging activities. In addition, hydrogen peroxide ($H_2O_2$)-induced C6 glial cells were treated with CM at $0.5-2.5{\mu}g/mL$ for measurement of cell viability, ROS production, and protein expression resulting from oxidative stress. RESULTS: The CM extract showed high scavenging activities against DPPH, ${\cdot}OH$, and NO radicals at concentration of $1,000{\mu}g/mL$. Treatment of CM with $H_2O_2$-induced oxidative stress in C6 glial cells significantly increased cell viability, and decreased ROS production. Cyclooxygenase-2 and inducible nitric oxide synthase protein expression was down-regulated in CM-treated groups. In addition, the protein expression level of phospho-p38 mitogen-activated protein kinase (p-p38 MAPK), phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular regulated protein kinases (p-ERK) in $H_2O_2$-induced C6 glial cells was down-regulated upon CM administration. CONCLUSION: CM exhibited radical scavenging activity and protective effect against $H_2O_2$ as indicated by the increased cell viability, decreased ROS production, down-regulation of inflammation-related proteins as well as p-p38, p-JNK, and p-ERK protein levels. Therefore, we suggest that CM could play the protective role from oxidative stress in glial cells.

• Korean Journal of Agricultural Science
• /
• v.49 no.1
• /
• pp.137-149
• /
• 2022

We investigated the effects of Cirsium japonicum var. maackii (CJM) against oxidative stress-induced C6 glial cells and cognitive impairment in mice. To evaluate the anti-oxidative effect of the extract and fractions from CJM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and nitric oxide (NO) assays were conducted in H₂O₂-treated C6 glial cells. Furthermore, we identified the protective mechanisms of CJM with a scopolamine-treated mice model. The results revealed that H₂O₂ decreased the cell viability in C6 glial cells, indicating that H₂O₂ induced oxidative stress in glial cells. However, CJM fractions significantly increased cell viability in H₂O₂-treated C6 glial cells, which suggested that CJM protected against oxidative stress. CJM extract and fractions also reduced ROS and NO production, which were increased by H₂O₂ in C6 glial cells. In particular, the EtOAc fraction from CJM (EACJM) effectively protected against oxidative stress by increasing the cell viability and decreasing ROS and NO. Therefore, we carried out further in vivo experiments with EACJM. Scopolamine caused increases of ROS, thiobarbituric acid reactive substances (TBARS), and NO production. However, EACJM effectively alleviated ROS, TBARS, and NO levels compared to scopolamine-injected mice. In addition, EACJM up-regulated protein expressions of superoxide dismutase and glutathione peroxidase, indicating that EACJM enhanced the antioxidative system. Our results demonstrated that CJM had protective effects against oxidative stress in glial cells and memory dysfunction in mice. Based on these results, we propose that CJM could be a potential AD preventive and therapeutic agent.

• The Korean Journal of Pain
• /
• v.36 no.1
• /
• pp.51-59
• /
• 2023

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague-Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0-4 hours (early phase) and 24-28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

• Journal of Veterinary Science
• /
• v.24 no.2
• /
• pp.26.1-26.11
• /
• 2023

Background: Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. Objectives: This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. Methods: Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. Results: The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme. In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B1 receptor antagonist, R 715, or the BK B₂ receptor antagonist, HOE 140. Conclusions: These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.