• Korean Journal of Veterinary Research
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• v.59 no.4
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• pp.201-205
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• 2019

This study presents neurogenesis and neuronal migration patterns of gamma-aminobutyric acid-ergic (GABAergic) neurons during mesencephalic development of mouse. After neurons from embryonic day (E) 10-16 were labelled by a single injection of 5-bromo-2'-deoxyuridine (BrdU), immunohistochemistry was performed. Neurogenesis were mainly generated in the mesencephalic region at E10 to E13. After E14, BrdU positive cells were observed only in the dorsal mesencephalon. GABAergic neurons were mainly originated in the ventrolateral region of the mesencephalon at the early embryonic stage, especially at E11 to E13. E10-labeled cells showed positive for GABAergic neuron in the basal plate of the mesencephalon at E13. At E15, GABAergic neurons were observed in the entire basal plate and some regions of the ventral and dorsal mesencephalon. They were present in the whole basal plate, the ventral and dorsal mesencephalon of E17, spreading more outward of the mesencephalon at P0. Our study demonstrates that major neurogenesis of GABAergic neurons occurs at E11 to E13. However, neuronal migration continues until neonatal period during mesencephalic development.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.261-267
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• 2015

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor ${\gamma}$ agonist, is known to regulate inflammatory process and to have neuroprotective effects against neurological disorders. In the present study, we examined the effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in the mouse hippocampus following intracerebroventricular injection of kainic acid (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the neuroprotective effect against KA-induced neuronal damage and attenuated the activations of astrocytes and microglia in the hippocampal CA3 region. In addition, MPO and $NF{\kappa}B$ immunoreactivities in the glial cells were also decreased in the PGZ-treated group. These results indicate that PGZ had anticonvulsant and neuroprotective effects against KA-induced excitotocix injury, and that neuroprotective effect of PGZ might be due to the attenuation of KA-induced activation in astrocytes and microglia as well as KA-induced increases in MPO and $NF{\kappa}B$.

• Molecules and Cells
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• v.38 no.4
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• pp.312-317
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• 2015

Depletion of intracellular zinc by N,N,N,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream pro-apoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.

• Journal of electromagnetic engineering and science
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• v.15 no.3
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• pp.123-128
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• 2015

Previously, we investigated extremely low-frequency magnetic fields (ELF-MFs) on diverse DNA damage responses, such as phosphorylated H2AX (${\gamma}H2AX$), comet tail moments, and aneuploidy production in several non-tumorigenic epithelial or fibroblast cell lines. However, the effect of ELF-MF on DNA damage responses in neuronal cells may not be well evaluated. Here, we investigated the effects of ELF-MF on the DNA damage responses in HT22 non-tumorigenic mouse neuronal cells. Exposure to a 60-Hz, 2 mT ELF-MF did not produce any increased ${\gamma}H2AX$ expression, comet tail moments, or aneuploidy formation. However, 2 mT ELF-MF transiently increased the cell number. From the results, ELF-MF could affect the DNA damage responses differently, depending on the cell lines.

• Molecules and Cells
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• v.37 no.7
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• pp.554-561
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• 2014

Lysophosphatidic acid (LPA) is a lipid growth factor that exerts diverse biological effects through its cognate receptors ($LPA_1-LPA_6$). $LPA_1$, which is predominantly expressed in the brain, plays a pivotal role in brain development. However, the role of $LPA_1$ in neuronal migration has not yet been fully elucidated. Here, we delivered $LPA_1$ to mouse cerebral cortex using in utero electroporation. We demonstrated that neuronal migration in the cerebral cortex was not affected by the overexpression of $LPA_1$. Moreover, these results can be applied to the identification of the localization of $LPA_1$. The subcellular localization of $LPA_1$ was endogenously present in the perinuclear area, and overexpressed $LPA_1$ was located in the plasma membrane. Furthermore, $LPA_1$ in developing mouse cerebral cortex was mainly expressed in the ventricular zone and the cortical plate. In summary, the overexpression of $LPA_1$ did not affect neuronal migration, and the protein expression of $LPA_1$ was mainly located in the ventricular zone and cortical plate within the developing mouse cerebral cortex. These studies have provided information on the role of $LPA_1$ in brain development and on the technical advantages of in utero electroporation.

• Molecules and Cells
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• v.19 no.3
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• pp.408-417
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• 2005

Nitric oxide (NO) occurs in various types of cells in the central nervous system. We studied the distribution and morphology of neuronal nitric oxide synthase (NOS)-containing neurons in the visual cortex of mouse and rabbit with antibody immunocytochemistry. We also compared this labeling to that of calbindin D28K, calretinin, and parvalbumin. Staining for NOS was seen both in the specific layers and in selective cell types. The densest concentration of intense anti-NOS immunoreactive (IR) neurons was found in layer VI, while the weak anti-NOS-IR neurons were found in layer II/III in both animals. The NOS-IR neurons varied in morphology. The large majority of NOS-IR neurons were round or oval cells with many dendrites coursing in all directions. Two-color immunofluorescence revealed that only 16.7% of the NOS-IR cells were double-labeled with calbindin D28K in the mouse visual cortex, while more than half (51.7%) of the NOS-IR cells were double-labeled with calretinin and 25.0% of the NOS-IR cells were double-labeled with parvalbumin in mouse. By contrast, 92.4% of the NOS-IR neurons expressed calbindin D28K while only 2.5% of the NOS-IR neurons expressed calretinin in the rabbit visual cortex. In contrast with the mouse, none of the NOS-IR cells in the rabbit visual cortex were double-labeled with parvalbumin. The results indicate that neurons in the visual cortex of both animals express NOS in specific layers and cell types, which do not correlate with the expression of calbindin D28K, calretinin or parvalbumin between the two animals.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.44-44
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• 2003

In previous reports, pVPSV.IGR2.1 transgenic mouse were described that brain tumor and lymphoma by reason of Vasopressin-SV40 T antigen. In this study, we produced pVPSV.IGR3.6 transgenic mouse that used pVPSV.IGR3.6 vector. Expression of transgene was vary different in transgenic mouse. We obtained 6 transgenic mouse line, moreover they had died at the age of 2~6 weeks without transmitting the transgene to their offspring, and had tumorigenesis on same location with pVPSV.IGR2.1 transgenic mouse. Only a founder mouse was investigated for expression of fusion gene. Here we extended this transgenic approach to the study of tumor progression. From the mouse, we confirmed brain tumor cell, after then cultured for investigate characterization. In this report, we demonstrate that reduction of survival rate in transgenic mouse fused vasopressin gene length, acquisition of brain tumor cell, composition with astrocyte cells and neuronal cells. Finally, cells had no change with increase of passage.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.105-105
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• 2003

In previous reports, pVPSV.IGR2.1 transgenic mouse were described that brain tumor and lymphoma by reason of Vasopressin-SV40 T antigen. In this study, we produced pVPSV.IGR3.6 transgenic mouse that used pVPSV.IGR3.6 vector. Expression of transgene was vary different in transgenic mouse. We obtained 6 transgenic mouse line, moreover they had died at the age of 2-6 weeks without transmitting the transgene to their offspring, and had tumorigenesis on same location with pVPSV.IGR2.1 transgenic mouse. Only a founder mouse was investigated for expression of fusion gene. Here we extended this transgenic approach to the study of tumor progression. From the mouse, we confirmed brain tumor cell, after then cultured for investigate characterization. In this report, we demonstrate that reduction of survival rate in transgenic mouse fused vasopressin gene length, acquisition of brain tumor cell, composition with astrocyte cells and neuronal cells. Finally, cells had no change with increase of passage.

• BMB Reports
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• v.52 no.2
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

• Clinical and Experimental Pediatrics
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• v.60 no.6
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• pp.181-188
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• 2017

Purpose: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality. Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical neuronal cells and astrocytes. Methods: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes (P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2, p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05). Conclusion: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting ERK pathways.