• Proceedings of the PSK Conference
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• 2002.04a
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• pp.140.2-140.2
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• 2002

• International Journal of Oral Biology
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• v.40 no.2
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.342-347
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• 2011

Background: Glial cells are involved in immune and inflammatory responses in the central nervous system (CNS). Glial cells such as microglia and astrocytes also provide structural and functional support for neurons. Migration and morphological changes of CNS cells are associated with their physiological as well as pathological functions. The secreted protein lipocalin-2 (LCN2) has been previously implicated in regulation of diverse cellular processes of glia and neurons, including cell migration and morphology. Methods: Here, we employed a zebrafish model to analyze the role of LCN2 in CNS cell migration and morphology in vivo. In the first part of this study, we examined the indirect effect of LCN2 on cell migration and morphology of microglia, astrocytes, and neurons cultured in vitro. Results: Conditioned media collected from LCN2-treated astrocytes augmented migration of glia and neurons in the Boyden chamber assay. The conditioned media also increased the number of neuronal processes. Next, in order to further understand the role of LCN2 in the CNS in vivo, LCN2 was ectopically expressed in the zebrafish spinal cord. Expression of exogenous LCN2 modulated neuronal cell migration in the spinal cord of zebrafish embryos, supporting the role of LCN2 as a cell migration regulator in the CNS. Conclusion: Thus, LCN2 proteins secreted under diverse conditions may play an important role in CNS immune and inflammatory responses by controlling cell migration and morphology.

• BMB Reports
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• v.57 no.4
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• pp.167-175
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• 2024

Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.103-123
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• 2010

Objectives : This study was to investigate the effect of several herbal prescriptions such as Tianwangbuxindan qu zhusha, Tianwangbuxindan, Wendantang, Guipitang on the level of $MT_1$ and $MT_2$ melatonin receptors in C6 glial cells. Methods : For this study, we exposed of C6 cells to several herbal prescriptions resulted in non-cytotoxic in various dose as measured by MTT assay, trypan blue count, morphology change and DAPI stain. Results : Tianwangbuxindan qu zhush and Tianwangbuxindan induced the levels of $MT_1$ melatonin receptor expression in a dose-dependent manner without altering the level of $MT_2$ melatonin receptor expression. However, the treatment with Wendantang, Guipitang don't effect of $MT_1$ and $MT_2$ melatonin receptor expression. Conclusions : This results suggest that Tianwangbuxindan can be a promising the regulation of melatonin receptor synthesis, and further studies will be needed to clarify the mechanism.

• International Journal of Stem Cells
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• v.16 no.1
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• pp.44-51
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• 2023

Background and Objectives: DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs). Methods and Results: We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs in vitro. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells. Conclusions: Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.

• Parasites, Hosts and Diseases
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• v.52 no.6
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• pp.613-619
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• 2014

Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.3
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• pp.19-39
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• 2008

Objectives : It has been reported that CG was effective in decreasing injury to neural tissues. To investigate neural responses in the injured spinal cord, an extract of CG was examined to determine its effect on neural responses in the injured spinal cords of rats. Methods : After CG treatment was applied to the spinal cord of rats given a contusion injury, the re-growth responses of injured neural tissues and corticospinal tract axons was observed by measuring the number of GAP-43, Cdc2, and phospho-Erk1/2 proteins, CST axons, GFAP-stained astrocytes, and Glial scarring in the injured spinal cord. Results : Levels of GAP-43, Cdc2, and phospho-Erk1/2 proteins were found to have increased in the injured spinal cord region. The number of GFAP-stained astrocytes also increased within and around the injury cavity. Glial scarring, which was identified by CSPG immunofluorescence staining, was reduced by CG treatment. Anterograde tracing by Dil dye showed that the elongation of the CST axons in the dorso-medial white matter area was almost completely prevented at the injury site. Collateral sprouting was observed in the spinal cord rostrally close to the injury site, and CG treatment further increased axonal arborization in the corresponding region. In vivo migration of CST axons and astrocytes using an implanted polymer tube system showed more of an increase in enhanced migration of axons and astrocytes in CG-treated group compared to the injury control group. Conclusions : These results suggest that CG activated neural responses - including astrocyte migration - and promotes axonal regenerative activity in the injured spinal cord area.

• Journal of Life Science
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• v.29 no.12
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• pp.1371-1377
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• 2019

Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H₂O₂-induced oxidative stress in the C6 glial cells. The H₂O₂-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H₂O₂-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H₂O₂ in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H₂O₂ treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.

• Journal of Applied Biological Chemistry
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• v.64 no.1
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• pp.69-74
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• 2021

Chronic alcohol is responsible for oxidative stress and neurodegenerative diseases such as dementia. In the present study, we investigated the antioxidant activity and protective effects of seed of Carthamus tinctorius L. on ethanol-induced C6 glial cells. Antioxidant effect of seed of C. tinctorius L. was measured by scavenging activity of 1,1-diphenyl-2-prcrylhydrazy (DPPH), hydroxyl radical (·OH), superoxide radical, and nitric oxide. The seed of C. tinctorius L. extract showed significant radical scavenging activities in a concentration-dependent manner. In particular, it revealed strong DPPH and ·OH scavenging activity, displaying more than 80% at 500 and 100 ㎍/mL, respectively. Treatment of 500 mM ethanol to C6 glial cell led to decline of cell viability and elevation of reactive oxygen species (ROS) generation. However, seed of C. tinctorius L.-treated groups significantly increased cell viability and decreased ROS levels, compared to ethanol-induced control group. These results suggest that seed of C. tinctorius L. would have protective effect against neuronal oxidative stress induced by alcohol.