• Journal of Life Science
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• v.17 no.4 s.84
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• pp.587-592
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• 2007

Manipulation of the mouse genome by activating or inactivating the gene has contributed to the understanding of the function of the gene in the subset of cells during embryonic development or postnatal period of life. Most of all, gene targeting, which largely depends on the availability of mouse embryonic stem (ES) cells, is the milestone of development of animal models for human disease. Recombinase-mediated genome modification (Cre-LoxP and Flp-Frt etc) and the ligand-dependent regulation system, more accurate and elaborate manipulation tools, have been successfully developed and applied to dissect the mechanisms governing complex biological processes and to understand the role of protein in temporal-and spatial aspects of development. As technologies concerning refined manipulation of mouse genome are developed, they are expected to open new opportunities to better understand the diverse in vivo functions of genes.

• Journal of Environmental Health Sciences
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• v.47 no.5
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• pp.446-453
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• 2021

Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

• Journal of Environmental Health Sciences
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• v.48 no.2
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• pp.106-115
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• 2022

Background: Current research suggests that humans are exposed to microplastics through consumption of foods and beverages, the airway route, and a variety of other means. Objectives: We evaluated oxidative stress and inflammation from polyethylene microplastics (PE-MPs) in the neonatal liver through intragastric administration or intratracheal instillation in pregnant mice. Methods: PE-MPs were administered from gestational day 9 to postnatal day 7. The intragastric administration group (0.01 mg/mouse/day or 0.1 mg/mouse/day) and intratracheal instillation group (6 ㎍/mouse/day or 60 ㎍/mouse/day) of PE-MPs were administered. After sacrifice, the oxidative stress and inflammation of the neonatal livers were measured. Results: As a result of the oxidative stress caused by PE-MPs in the neonatal livers, glutathione peroxidase decreased in a concentration-dependent manner in the intragastric administration group compared to the control group and intratracheal instillation decreased in high concentration PE-MPs. The catalase level increased at high concentrations of intragastric administration and intratracheal instillation. To confirm the level of inflammation caused by PE-MPs, monocyte chemoattractant protein-1 and tumor necrosis factoralpha were increased compared to the control group except for intratracheal intilation-high concentration PEMPs. The C-reactive protein level was decreased by intragastric administration compared to the control group and intratracheal instillation was increased compared to the control group. Conclusions: Despite the difficulty in comparing the toxic intensity between intragastric administration and intratracheal instillation of PE-MPs, our study revealed that oxidative stress and inflammation were induced in the neonatal liver. However, it is necessary to evaluate the toxic effects of microplastics on various organs as well. Overall, the present study indicates that the evaluation of toxic effects of long-term microplastic exposure, potential of microplastic toxicity on next-generation offspring and toxicity mechanism in human should be considered for further investigations.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.113-125
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• 2023

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.173-180
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• 2006

Microglial activation is thought to play a role in the pathogenesis of many brain disorders. Therefore, understanding the response of microglia to noxious stimuli may provide insights into their role in disorders such as stroke and neurodegeneration. Many genes involved in this response have been identified individually, but not systematically. In this regards, the microarray system permitted to screen a large number of genes in biological or pathological processes. Therefore, we used microarray technology to evaluate the effect of oxygen glucose deprivation (OGD) and reperfusion on gene expression in microglia under ischemia-like and activating conditions. Primary microglial cultures were prepared from postnatal mice brain. The cells were exposed to 4 hrs of OGD and 1 h of reperfusion at $37^{\circ}C$. Isolated mRNA were run on GeneChips. After OGD and reperfusion, ＞2-fold increases of 90 genes and ＞2-fold decrease of 41 genes were found. Among the genes differentially increased by OGD and reperfusion in microglia were inflammatory and immune related genes such as prostaglandin E synthase, $IL-1{\beta}$, and $TNF-{\alpha}$. Microarray analysis of gene expression may be useful for elucidating novel molecular mediators of microglial reaction to reperfusion injury and provide insights into the molecular basis of brain disorders.

• The Journal of Korean Society of Virology
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• v.28 no.2
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• pp.183-192
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• 1998

DNA methylation degree in the several murine brain and liver genes of different ages and after scrapie infection have been examined by using methylation-sensitive restriction endonuclease digestion. We found that the methylation of c-fos and c-myc in the brain and liver was increased during the late fetal to one month postnatal developmental periods. However, those of the SGP-2, $S100{\beta}$, APP950, PrP, and APLP1 genes were decreased at the same periods. The comparison of the DNA methylation patterns between scrapie infected brains and controls demonstrated there is no significant difference in methylation degree of scrapie-infected brains. These observations indicate that DNA methylation might be importantly related to the aging process. The scrapie-infected murine brain was not significantly developed more senescent than the same age-controls did.

• The Journal of the Korean dental association
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• v.14 no.3
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• pp.297-305
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• 1976

신생의 Balb/C strain 백서20두를 사용하였고, 실험군과 대조군으로 구분하여 실험군에는 5-fluorouracil의 체중 25 mg/kg씩 2회를 복강내주사하였다. 실험군가 대조군에 모두 희생 2시간전에 체중그람당 5μ Ci의 thymidine-H³ (Specific activity는 9.0 Ci/mM 이상)를 복강내 주사하였다. 각군은 5-fluorouracil 최종 주사후 1, 3, 7, 14, 21일 간격으로 희생시키고, 두부를 4% formalin에 고정하였다. 조직을 0.5M EDTA에 탈회하고 parlodion과 paraplast에 이중 매몰을 하여 Parasagittal serial section 을 10μ의 절편을 만든 후 자기방사용표본을 제작하였다. 그 결과는 다음과 같다. 1. 5-fluorouracil이 백서설의 기저세포층의 핵산합성 및 단백합성에 미치는 영향은 실험초일인 제 1일부터 억제하기 시작하여 (80.9%) 제3일 76.9%이고, 제 7일이 가장 극심하고 (66.2%) 그후부터는 다소회복되기 시작하여 제14일이 92/3%이고, 제21일인 98.9%로서 서의 대조군수치에 접근하였다. 2. 5-fluorouracil은 설유두중 nallate papillae 성장에 가장 억제적 현상을 보였고, 그 다음이 fungiform papillae, filiform papillae의 순위였다. 3. 5-fluorouracil 이 백서설의 기저세포층의 핵산합성을 억제함을 알 수 있고, 아울러 백서설의 조기정상 발육에 영향을 줌울 알 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.39-49
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• 2021

High fructose diet is associated with the global metabolic syndrome (MtS) pandemic. MtS develops in early life, depending on prenatal and postnatal nutritional status. We hypothesized that ovariectomy increases the chances of developing MtS in adult offspring following high fructose intake by the mother. Pregnant C57BL/6J mouse dams drank water with or without 20% fructose during pregnancy and lactation. After weaning, the pups were fed regular chow. The offspring were evaluated until they were 7 months of age after the mice in each group, both sexes, were gonadectomized at 4 weeks of age. The offspring (both sexes) of the dams who had high fructose intake developed MtS. In the offspring of dams who drank tap water, orchiectomy increased the body weight gain and body fat accumulation, while ovariectomy increased the body fat accumulation as compared to the sham controls. In the offspring of dams with high fructose intake, orchiectomy decreased the body weight gain, body fat accumulation, visceral adiposity, and glucose intolerance, while ovariectomy exacerbated all of them as compared to the sham operations. These data indicate that ovariectomy encourages the development of MtS in adult offspring after maternal high fructose intake, while orchiectomy prevents the development of MtS. The sex difference indicates that male and female sex hormones play contradictory roles in the development of MtS.

• The korean journal of orthodontics
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• v.34 no.2 s.103
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• pp.143-152
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• 2004

It has not been elucidated whether the initiation of condylar development of the mandible is related with the periosteum of the mandible, or if it derives from a separate programmed blastema not related with the mandible. Also, although the mandibular condylar cartilage is known to promote growth, few studies have dealt with molecular-biologic mechanisms such as the expression of specific genes according to the differentiation of the mandibular condyle. To elucidate the unique cellular characteristics, development, and differentiation process of the mandibular condyle, an examination of expressions of genes characteristic of cartilage and bone were carried out using RT-PCR and mRNA in situ hybridization. 1. Type? collagen mRNA was detected with type II collagen mRNA in the differentiation and growth process of the cartilage of the mandibular condyle. TypeII collagen mRNA was demonstrated in the whole resting md upper part of the poliferative zone, whereas type II collagen mRNA was observed in the resting, proliferative and upper hypertrophic cartilage zone of the mandibular condyle. 2. The condylar cartilage rapidly increased in size due to the accumulation of hypertrophic chondrocytes as characterized by the expression of type II collagen mRNA during postnatal development. 3. BMP-4 mRNA was present in the anlage of the future condylar process and also in the ossifying mandibular body. 4. IHH mRNA was limited exclusively to the lower part of the proliferative zone and the upper part of the hypertrophic cartilage zone during condylar development. These findings were different from those in the growth-plate cartilage of the long bone, indicating a characteristic feature of the differentiation of the chondrocytes in the condylar cartilage present in prenatal and postnatal development. Furthermore, it was also suggested that chondroblasts of condylar cartilage rapidly differentiate into hypertrophic chondrocytes with increased functional Load force such as muscle activity and mastication.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.395-400
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• 2001

The present study analyze the morphological aspects of the cerebrum of mice with prenatal exposure to high and low dose (0.5, 1, 2 Gy) of $\gamma$-radiation on gestation day 12 or 16. The animal were allowed to give birth and the offspring were sacrificed at postnatal days 28 for gross and microscopic examination of cerebrum. Their body weight, brain weight, brain length, brain width, cortical thickness and area of cingulum bundle were examined. The histological and planimetric analysis were performed observing coronal sections. The gross malfomation (microcephaly) and abnormality of cortical architecture were prominent after exposure to 2 Gy on day 12 of gestation. significant dose-related reductions in body weight, brain weight, brain size were found in all irradiated groups. A significant change was found in thickness of the cerebral cortex and area of the cingulum bundle in the groups exposed to 0.5 Gy or more. There was no difference a lamina patter of six layers in cerebral cortex between the control and irradiated groups, but cell packing density increased significantly in the group exposed to 1 Gy or more. These results suggested that dose as low as 0.5 Gy could cause a morphologically reduce change in developing mouse cerebrum and exposure on day 12 of gestation to $\gamma$-irradiation is a particularly sensitive phase in causing malformation and abnormality of central nerve system.