• 한국동물생명공학회지
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• 제38권2호
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• pp.77-83
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• 2023

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.8.1-8.14
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• 2018

We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.

• 대한수의학회지
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• 제45권2호
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• pp.139-149
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• 2005

In order to study about the lobule and layer formation and cell migration of the mouse cerebellum from at the birth to 15th day effected by 2.5, 5 and 10 Gy r-raddiation at the 19th pregnancy. The routine tissue preparation and staining procedure, Immunohistochemical staining method by the several antibody and western brotting method were utilized from the birth to the15th day. The results were as followings. 1. The body and cerebellum weights were more slowly increase of the the 2.5 Gy, 5 Gy and 10 Gy irradiation group compare to the control group, and the health condition of the 2.5 Gy group was a little bad. but the 10 Gy group was more severe and begun to die from the 12th day after birth. 2. The thickness, proliferation and migration of the 2.5, 5 and 10 Gy irradiated external granular cells from the maginal zone to the medullary area forming the molecular layer from the 6th day to the 15th day after birth were thinner, weaker and more slower according to the radiated dosages than the control group in the cresyl violet staining. 3. The proliteration, migration and lobulation of the 5 Gy radiated groups from the first day to the 15th day after birth were more weak, incomplete and irregular shape in the immunostaining with Dab, Cdk5, P35, calbindin and Zebrin antibody. 4. In the western blotting analysis using the Reelin, Dab, Cdk5 and P35 antibody. The Bands were in the 60 KD, 80 KD, 33 KD and 35 KD, and there were no differences between the control and irradiated groups in the molecular band except the Reelin. 5. As a results, the proliferation and migration of the outer granular and purkinje cells, and lobulation of the cerebellum by the several dosaege of the ${\gamma}$-ray radiation were proportionally incomplete according to dosage.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.386-389
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• 2015

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

• 대한소아신경학회지
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• 제25권3호
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• pp.200-203
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• 2017

척수소뇌실조는 임상적으로 다양하게 나타나는 보통염색체 우성신경변성 (혹은 퇴행성) 질환군으로서, 소뇌의 들과 날의 경로를 분열시켜 소뇌 실조를 일으키는 것으로 알려져 있다. 전형적인 임상증상은 30에서 40대에 발현되기 시작하고, 보행실조, 불분명 발음, 시력 이상, 사지의 조화운동 불능, 안구 움직임 제한, 인지 장애 등 다양한 증상의 조합을 특징으로 한다. 본 증례의 환아에서는 exome sequencing을 통하여 SPTBN2 (p.Glu1251Gln)의 새로운 이형접합 돌연변이를 발견하였으며 이것이 SCA5의 원인으로 밝혀졌다. 증례의 환아는 3년 5개월 때 발달지연을 주소로 본원에 내원하였다. 발달지연을 평가하기 위해 베일리 발달 검사에서 모든 영역에서 현저한 지연이 확인되었다. 본원 내원 1년 전 시행한 뇌자기공명영상에서 백샐질형성장애와 약간의 소뇌 위축이 보였다. 잠재적인 유전질환을 의심하여 진단 목적으로 전체엑솜염기서열분석을 시행하였고 결과적으로 SPTBN2의 새로운 이형접합 돌연변이 (p.Glu1251Gln) 가 SCA5의 원인 돌연변이로 사료된다. 척수소뇌실조에서 유전자의 역할을 명확하게 규명하기 위해서는 전체엑솜염기서열 분석을 포함한 다양한 방법을 통한 유전자 연구가 필요할 것으로 사료된다.