• Korean Journal of Biological Psychiatry
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• v.22 no.2
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• pp.34-39
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• 2015

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. A serious problem such as suicide is commonly occurring in the patients with depression. Till now, the monoamine hypothesis has been the most popular theory of pathogenesis for depression. However, the more specific pathophysiology of depression and cellular molecular mechanism underlying action of commercial antidepressants have not been clearly defined. Several recent studies demonstrated that glial cells, especially astrocytes, are a promising answer to the pathophysiology of depression. In this article, current understanding of biology and molecular mechanisms of glial cells in the pathology of mood disorder and new research on the pathophysiology of depression will be discussed.

• Journal of Life Science
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• v.29 no.12
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• pp.1329-1336
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• 2019

Subventricular zone (SVZ) in the brain contains neural stem cells (NSCs) which self-renew and differentiate to neurons and glial cells during postnatal period and throughout adulthood. Since fate decision to either proliferation or differentiation has to respond to intracellular and extracellular conditions, many intrinsic and extrinsic factors are involved. Among them, mitochondria have been reported to participate in fate decision of NSCs. In our previous report, we showed that long-term treatment of a mitochondrial inhibitor rotenone greatly inhibited neurogenesis. In this study, we examined the effects of short-term treatment of rotenone on SVZ NSCs. We found that (1) even one-day treatment of rotenone significantly reduced neurogenesis and earlier time points seemed to be more sensitive to rotenone, (2) a number of Mash1+ transit amplifying cells was decreased by one-day treatment of rotenone, (3) short-term treatment of rotenone eliminated most of the differentiated Tuj1+ neurons and Olig2+ oligodendrocytes, while glial fibrillary acidic protein (GFAP)+ astrocytes were not affected, and (4) sulfiredoxin 1 (Srxn1) gene expression was increased after one-day treatment of rotenone, indicating activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. All these results confirm that functional mitochondria are necessary during differentiation to neurons or oligodendrocytes as well as maintenance of neurons after differentiation. Also, these data suggest that temporary exposure to mitochondrial inhibitor such as rotenone might have long-term effects on neurogenic potential of NSCs.

• Applied Microscopy
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• v.29 no.1
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• pp.57-66
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• 1999

The nervous tissue in the cerebral ganglion of Korean planaria was observed using electron microscope. The obtained results are as follows: A cerebral ganglion is composed of the nerve cells, neurosecretory cells, neuroglial cells and neuropils. The nerve cells are round or ovoidal-shaped cells (diameter, $5{\mu}m$), which has a large ellipsoidal nucleus containing the evenly developed heterochromatin. Their cytoplasms were found to be relatively simple, because of their undeveloped cell organelles. The neurosecretory cells are long and ellipsoid or spindle-shaped cells, where there were found a large ellipsoidal nucleus and cytoplasm filled with secretory granules (diameter, 60 nm). The neuroglial cells were seldom observed. They are spindle-shaped cells (size, $6\times0.8{\mu}m$), which were observed mainly among the nerve fibers. The neuropils are formed by the nerve fibers and nerve endings which are filled with mitochondria, neurotubules and secretory granules of four kinds (high electron dense granules of sizes 75 nm, 50 nm and 37 nm, and electron lucent granule of size 30 nm etc.). These granular vesicles are divided into single vesicle type and compound vesicle type in the nerve terminals, and neuronal synapses were observed to be the axo-dendritic and dendro-dendritic synapse type.

• Journal of Nutrition and Health
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• v.50 no.1
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• pp.25-31
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• 2017

Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.33 no.5
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• pp.429-435
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• 2023

Epidemiological studies suggest that maternal infection, maternal stress, and environmental risk factors during pregnancy increase the risk of brain development abnormalities associated with cognitive impairment in the offspring and increase susceptibility to schizophrenia and autism spectrum disorder. Several animal models have demonstrated that maternal immune activation (MIA) is sufficient to induce abnormal brain development and behavioral defects in the fetus. When polyinosine:polycytodylic acid (poly I:C) or lipopolysaccharide (LPS), which is commonly used in maternal immune activation animal models, was introduced into a pregnant dam, an increase in pro-inflammatory cytokines and microglial activity was observed in the offspring's brain. Microglia are brain-resident immune cells that play a mediating role in the central nervous system, and they are responsible for various functions, such as phagocytosis, synapse formation and branching, and angiogenesis. Several studies have reported that microglia are activated in MIA offspring and influence offspring behavior through interactions with various cytokines. In addition, it has been reported that they play an important role in brain circuits through interactions with neurons and astrocytes. However, there is controversy concerning whether microglia are essential to brain development or lead to behavioral defects, and the exact mechanism remains unknown. Therefore, for the potential diagnosis and treatment of brain developmental disorders, a functional study of microglia should be conducted using MIA animal models.

• The Journal of the Korea Contents Association
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• v.11 no.2
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• pp.341-352
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• 2011

The purpose of this study was carried out to investigate the effect of electroacupuncture on reactive gliosis expressing GFAP in rat with transient global cerebral ischemia. Subjects were randomly divided into two groups, a control group and a electroacupuncture group on ST36, LI11 and SP9 with 2 Hz and 1 mA. The rats were sacrificed on 1, 3 and 7 days after transient cerebral ischemia using ligation of left common carotid artery. After making brain slide sections, they were immunostained with GFAP antisera(1:2,500). The results were as follows: The numbers of astrocytes of electroacupuncture group were decreased than those of control group at every 1, 2 and 7 days. Especially, the numbers of astrocytes at 3 days(p<0.01) and 8 days(p<0.05) were different statistically. And astrocytes had resting, hypertrophic and moving types on cerebral cortex. The decrease of numbers of astrocytes expressing GFAP showed that electroacupuncture could localise and minimize the brain damage by transient cerebral ischemia and cause brain cell plasticity.

• Journal of Life Science
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• v.33 no.6
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• pp.455-462
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• 2023

During pregnancy, maternal immune activation (MIA) from infection increases the risk of neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. MIA induced by polyinosinic-polycytidylic acid (poly (I:C)) and lipopolysaccharide (LPS) in animal experiments has led to offspring with abnormal behaviors and brain development. In addition, it has recently been reported that microglia, which reside in the brain and function as immune cells, play an important role in behavioral abnormalities and brain development in MIA-induced offspring. However, the underlying mechanism remains unclear. In this study, we investigated whether microglia-specific inhibition of GPR56, a member of the G protein-coupled receptor (GPCR) family, causes behavioral abnormalities in brain development. First, MIA induction did not affect the microglia population, but when examining the expression of microglial GRP56 in MIA-induced fetuses, GPR56 expression was inhibited between embryonic days 14.5 (E14.5) and E18.5 regardless of sex. Furthermore, microglial GPR56-suppressed mice showed abnormal behaviors in the MIA-induced offspring, including sociability deficits, repetitive behavioral patterns, and increased anxiety levels. Although abnormal cortical development such as that in the MIA-induced offspring were not observed in the microglial GPR56-suppressed mice, their brain activity was observed through c-fos staining. These results suggest that microglia-specific GPR56 deficiency may cause abnormal behaviors and could be used as a biomarker for the diagnosis and/or as a therapeutic target of behavioral deficits in MIA offspring.

• Development and Reproduction
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• v.12 no.1
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• pp.87-95
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• 2008

Neural stem/precursor derived from pluripotent human embryonic stem cells (hESCs) has considerable therapeutic potential due to their ability to generate various neural cells which can be used in cell-replacement therapies for neurodegenerative diseases. However, production of neural cells from hESCs remains technically very difficult. Understanding neural-tube like rosette characteristic neural precursor cells from hESCs may provide useful information to increase the efficiency of hESC neural differentiation. Generally, neural rosettes were derived from differentiating hEBs in attached culture system, however this is time-consuming and complicated. Here, we examined if neural rosettes could be formed in suspension culture system by bypassing attachment requirement. First, we tested whether the size of hESC clumps affected the formation of human embryonic bodies (hEBs) and neural differentiation. We confirmed that hEBs derived from $500{\times}500\;{\mu}m$ square sized hESC clumps were effectively differentiated into neural lineage than those of the other sizes. To induce the rosette formation, regular size hEBs were derived by incubation of hESC clumps($500{\times}500\;{\mu}m$) in EB medium for 1 wk in a suspended condition on low attachment culture dish and further incubated for additional $1{\sim}2$ wks in neuroectodermal sphere(NES)-culture medium. We observed the neural tube-like rosette structure from hEBs after $7{\sim}10$ days of differentiation. Their identity as a neural precursor cells was assessed by measuring their expressions of neural precursor markers(Vimentin, Nestin, MSI1, MSI2, Prominin-1, Pax6, Sox1, N-cadherin, Otx2, and Tuj1) by RT-PCR and immunofluorescence staining. We also confirmed that neural rosettes could be terminally differentiated into mature neural cell types by additional incubation for $2{\sim}6$ wks with NES medium without growth factors. Neuronal(Tuj1, MAP2, GABA) and glial($S100{\beta}$ and GFAP) markers were highly expressed after $2{\sim}3$ and 4 wks of incubation, respectively. Expression of oligodendrocyte markers O1 and CNPase was significantly increased after $5{\sim}6$ wks of incubation. Our results demonstrate that rosette forming neural precursor cells could be successfully derived from suspension culture system and that will not only help us understand the neural differentiation process of hESCs but also simplify the derivation process of neural precursors from hESCs.

• Journal of Life Science
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• v.23 no.1
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• pp.125-130
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• 2013

Calponin 3 is an F-actin-binding protein and plays a key role in regulating spine plasticity and synaptic activity in neurons. Unlike the other subtypes, calponin 1 and 2, which are expressed in smooth and cardiac muscle cells, calponin 3 is highly expressed in the brain. The goal of this study was to elucidate the spatiotemporal expression pattern of calponin 3 following repeated administration of 3-nitropropionic acid in mice. The repeated administration of 3-nitropropionic acid generated necrotic neuronal cell death in the striatum. Calponin 3 was up-regulated in the neuroprotective penimbral region from 1.5 days after the last injection and thereafter. Double immunofluorescence study revealed that calponin 3 was induced in GFAP-positive astrocytes. These results suggest that calponin 3 induction in the neuroprotective penumbral area following 3-nitropropionic acid intoxication may play a key role in reactive astrogliosis in the striatum.

• International Journal of Oral Biology
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• v.39 no.1
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• pp.49-56
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• 2014

We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, $40{\mu}L$) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a $P2X_{2/3}$ receptor antagonist, 5-BDBD, a $P2X_4$ receptor antagonist, or A438079 hydrochloride, a $P2X_7$ receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS ($25{\mu}g$) or A438079 (25 or $50{\mu}g$) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central $P2X_7$ receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central $P2X_7$ receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.