• The Journal of Korean Medicine
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• v.23 no.3
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• pp.145-163
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• 2002

Objectives: The purpose of this investigation was to evaluate the effects of Woohwangcheongsim-won and to study the mechanism for neuronal death protection in hypoxia with Embryonic day 20 (E20) cortical cells of a rat (Sprague Dawley). Methods: E20 cortical cells were dissociated in neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Woohwangcheongsim-won was added to the culture media for 24 hrs or 72 hrs. On 17 DIV, cells were given a hypoxic shock and further incubated in normoxia for another three days. On 20 DIV, Woohwangcheongsim-won's effects for neuronal death protection were evaluated by LDH assay, propidium iodide stain and phospho-H2AX immunostain and the mechanisms were studied by Bcl-2, Bak, Bax, caspase family, PKCα, ca1pain I. Results & Conclusions : 1. This study indicated that Woohwangcheongsim-won's effects for neuronal death protection in hypoxia were confirmed by LDH assay, propidium iodide stain and phospho-H2AX immunostain in culture method of Embryonic day 20(E20) cortical neuroblasts. 2. Woohwangcheongsim-won's mechanisms for neuronal death protection in hypoxia are to reduce the membrane damage fraction, to restrain DNA truncate, to restrain inflow of cytochrome c into cellularity caused by Bak diminution, to reduce the caspase cascade intiator caspase-8 and the effector caspase-3, to reduce the calpain I activity and to increase PKCand its activity in the membrane fraction. (J Korean Oriental Moo 2002;23(3):145～163)

• Applied Microscopy
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• v.26 no.2
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• pp.137-155
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• 1996

The development of the ganglia of the trachea was studied by electron microscopy in human fetuses ranging from 40 mm to 260 mm crown rump length. At 40 mm fetus, the tracheal ganglia was observed in the submucosa of the trachea. The primitive ganglia consisted of neuroblasts, undifferentiated cells, and unmyelinated nerve fibers. At 50 mm fetus, the neuroblast and their processes in the tracheal ganglia ware ensheathed by the bodies or processes of satellite cells. The cytoplasm of the neuroblast contained rough endoplasmic reticulum, mitochondria, Golgi complex, and ribosomes. At 70 mm fetus, cholinergic and adrenergic axon terminals were observed. Cholinergic axon terminals with agranular vesicles were abundant in the tracheal ganglia with increasing age. During next prenatal stage from 100 mm fetus, the ganglion cells and its processes were completely covered by a thin processes of the satellite cells. Unmyelinated nerve fibers were also completely ensheathed by processes of Schwann cell. Synaptic contacts between the cholinergic axon and dendrite of ganglion cells and a few dendrodendritic synapses were first observed at 100 mm fetus. The granule-containing cells were first identified in the tracheal ganglia at 200 mm fetus. These findings indicate that tracheal ganglia of human fetus resembles other parasympathetic and sympathetic ganglia, but not the enteric ganglia.

• Molecules and Cells
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• v.26 no.6
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• pp.576-582
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• 2008

Nervous system development takes place after positional information has been established along the dorsal-ventral (D/V) axis. The initial subdivision provided by a gradient of nuclear dorsal protein is maintained by the zygotic genes expressed along the D/V axis. In this study, an investigation was conducted to determine the range of Dpp function in repressing the expression of eagle (eg) that is present in intermediate neuroblasts defective (ind) and muscle specific homeobox (msh) gene domain. eg is expressed in neuroblast (NB) 2-4, 3-3 and 6-4 of the msh domain, and NB7-3 of the ind domain at the embryonic stage 11. In decapentaplegic (dpp) loss-of-function mutant embryos, eg was ectopically expressed in the dorsal region, while in dpp gain-of-function mutants produced by sog or sca-GAL4/UAS-dpp, eg was repressed by Dpp. It is worthy of note that Dpp produced from sim;;dpp embryos showed that Dpp could function at long range. However, Dpp produced from en-GAL4/UAS-dpp or wg-GAL4/UAS-dpp primarily acted at short-range. This result demonstrated that this discrepancy seems to be due to the repression of Dpp to EGFR signaling in sim;;dpp embryos. Taken together, these results suggest that Dpp signaling works at short-range, but can function indirectly at long-range by way of repression of EGFR signaling during embryonic neurogenesis.

• The Journal of Korean Medicine
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• v.23 no.4
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• pp.125-139
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• 2002

Objectives: The purpose of this investigation is to evaluate the effects of Woohwangcheongsim-won and to study the mechanism for neuronal death protection in OGD (oxygen-glucose deprivation) model with embryonic day 20 (E20) cortical cells of a rat (Sprague Dawley). Methods: E20 cortical cells were dissociated in neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Woohwangcheongsim-won was added to the culture media for 72 hrs. On 17 DIV, cells were given an oxygen-glucose deprivation shock (2hrs and 4hrs) and further incubated in normoxia for another three days. On 20 DIV, Woohwangcheongsim-won's effects for neuronal death protection were evaluated by LDH assay and the mechanisms were studied by Bcl-2, Bak, Bax, caspase family. Results & Conclusions: 1. This study indicates that Woohwangcheongsim-won's effects for neuronal death protection in OGD model is confirmed by LDH assay in culture method of embryonic day 20(E20) cortical neuroblasts. 2. Woohwangcheongsim-won's mechanisms for neuronal death protection in OGD model are to restrain inflow of cytochrome c into cellularity caused by Bcl-2 increase (2hrs and 4hrs), to reduce the caspase cascade initiator caspase-8 (4hrs).

• Applied Microscopy
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• v.26 no.3
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• pp.329-348
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• 1996

The prenatal development of lateral motor columns in the lumbar spinal cord was studied by electron microscopy in human embryos and fetuses ranging from 9 mm to 260 mm crown-rump length ($5{\sim}30$ weeks of gestational age). At 9 mm embryo, the lateral motor column were developed from ventro-lateral projection into the marginal layer and composed of primitive neuroblasts. At 20 mm embryo the primitive motor neurons were packed closely together and could readly be distinguished from primitive glioblasts by a presence of large nuclei. The primitive multipolar neurons were observed in lateral motor column at 40 mm fetus. At 80 mm fetus multipolar neurons were characterized by their many dendrites and axons in the vicinity of motor neuron perikarya. At 260 mm fetus, the motor neurons were large and contained all intracytoplasmic structures in the cytoplasm which were also found in mature motor neuron in lateral motor column. The first axo-dendritic synapses found at 40 mm fetus and increased in number throughout fetal development. Axo-somatic synapses with spherical vesicles were first observed at 80 mm fetus. A few axo-somatic synapses were found at next prenatal stages. Axo-dendritic and axo-somatic synapses contained mixed populations of spherical and flattened vesicles by 120 mm fetus. These findings indicate that axo-dendritic synapses develop prior to axo-somatic synapses in the spinal cord during neurogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.251-256
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• 2009

Previous observations suggest that Bis, a Bcl-2-binding protein, may playa role the neuronal and glial differentiation in vivo. To examine this further, we investigated Bis expression during the in vitro differentiation of P19 embryonic carcinoma cells induced by retinoic acid (RA). Western blotting and RT-PCR assays showed that Bis expression was temporarily decreased during the free floating stage and then began to increase on day 6 after the induction of differentiation. Double immunostaining indicated that Bis-expressing cells do not express several markers of differentiation, including NeuN, MAP-2 and Tuj-1. However, some of the Bis-expressing cells also were stained with GFAP-antibodies, indicating that Bis is involved glial differentiation. Using an shRNA strategy, we developed bis-knock down P19 cells and compared them with control P19 cells for the expression of NeuroD, Mash-1 and GFAP during RA-induced differentiation. Among these, only GFAP induction was significantly attenuated in Pl9-dnbis cells and the population showing GFAP immunoreactivity was also decreased. It is noteworthy that distribution of mature neurons and migrating neurons was disorganized, and the close association of migrating neuroblasts with astrocytes was not observed in P19-dnbis cells. These results suggest that Bis is involved in the migration-inducing activity of glial cells.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.259-264
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• 1985

Neuroblastoma is the most common extracranial solid tumor of childhood which presents various clinical symptoms depending on the primary and metastatic sites. However, it has been rarely reported that sudden onset of blindness was the chief complaint of neuroblastoma. A four years old boy was admitted to the Yeungnam University Hospital with the chief complaint of a sudden onset of blindness due to a distant metastasis of abdominal neuroblastoma to the sphenoid sinus. On admission, both side pupils were dilated without light reflex, fundoscopy showed pale optic disk, electroretinogram was subnormal and visual evoked potential showed no response. The liver was palpable in $3{\frac{1}{2}}$ finger breadth from the right costal margin and adult fist sized mass was palpable in the right flank. Skull X-ray showed destructed sphenoid bone and clinoid process and brain CT scan showed tumor mass in the sphenoid sinus and left orbit. Ultrasonogram and CT scan of the abdomen showed large tumor masses around the right kidney and para-aortic and retropancreatic lymph node. IVP showed displaced right calyceal system with preserved contour. Left supraclavicular lymph node which appeared after admission was biopsied and it showed poorly differentiated neuroblasts. He was treated according to the multiagent chemotherapy schedule for stage IV neuroblastoma patient of children's cancer study group. Abdominal tumor masses and sphenoid sinus mass were markedly reduced after 2 courses of the combination chemotherapy of cyclophosphamide, vincristine, DTIC, adriamycin and VM-26. Eventhough the blindness was not improved, the patient has been in good clinical condition.

• Molecules and Cells
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• v.42 no.2
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• pp.123-134
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• 2019

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals through specific G protein-coupled receptors, known as $LPA_{1-6}$. For one of its receptors, $LPA_1$ (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5'RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5' of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5' regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa E-box binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings.

• BMB Reports
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• v.56 no.9
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• Anatomy and Cell Biology
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• v.56 no.1
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• pp.69-85
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• 2023

Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.