• Title/Summary/Keyword: mouse brain

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Genetically engineered brain drug delivery vector through the blood-brain barrier

  • Seo, Kyung-Hee;Kang, Young-Sook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.192-192
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    • 1998
  • The blood - brain barrier (BBB) expresses high concentrations of transferrin receptor, and it was revealed that anti-transferrin receptor mouse monoclonal antibody (OX26) undergoes transcytosis through the BBB. This property allows the OX26 to serve as a brain drug delivery vector. In an attempt to produce broadly useful targeting agents, genetic engineering and expression techniques have been used to produce antibody-avidin (AV) fusion protein (OX26 IgG3C$\_$H/3-AV). In the present study we estimated the BBB permeability and stability of genetically engineered vector.

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Regulation of LPS-induced Nitric Oxide Synthase Activity by Cigarette Smoke in Mouse Brain

  • Moon, Ja-Young;Lim, Heung-Bin;Sohn, Hyung-Ok;Lee, Young-Gu;Hyun, Hak-Chul;Shin, Hantae;Lee, Dong-Wook
    • Toxicological Research
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    • v.22 no.3
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    • pp.245-251
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    • 2006
  • Nitric oxide(nitrogen monoxide, NO) plays important physiological roles, but excessive generation can be toxic. NO is present in cigarette smoke at up to 1,000 ppm, and probably represents one of the greatest exogenous sources of NO to which humans are exposed. We investigated whether cigarette smoking reduces the production of endogenous NO and whether it influences the action of lipopolysaccharide(LPS) to induce nitric oxide synthase activity in mouse brain. Mice(C57BL6/J) were exposed to cigarette smoke for 8 weeks. LPS was injected intraperitoneally in single or combination with the exposure to cigarette smoke. Six hours after the injection of LPS, mice were sacrificed and sera and brains were collected. Serum concentrations of nitrate and nitrite were not charged by 4-week smoke exposure, but were significantly increased by 6 and 8 weeks of smoke exposure. Interestingly, cigarette smoke reduced the elevation in serum nitrate and nitrite concentrations produced by LPS after 4-week smoking exposure. NO synthase(NOS) activity in brain was upregulated by LPS-administration. However, cigarette smoke exposure remarkably and consistently decreased the LPS-induced activity in mouse brain. This result suggests that cigarette smoking may affect against overproduction of the endogenous NO by LPS through the inhibition of NOS activity induced by LPS in brain or by modulation of the LPS action for the induction of NOS activity. We also suggest the possibility that the exogenous NO evolved in cigarette smoke enables feedback inhibition of NOS activity or other possibility that it attenuates the toxicity of endotoxin LPS in vivo by unknown mechanisms, which should be further studied.

Neonatal influenza virus infection affects myelination in influenza-recovered mouse brain

  • Kim, Jin Hee;Yu, Ji Eun;Chang, Byung-Joon;Nahm, Sang-Soep
    • Journal of Veterinary Science
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    • v.19 no.6
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    • pp.750-758
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    • 2018
  • Influenza virus infection is a zoonosis that has great socioeconomic effects worldwide. Influenza infection induces respiratory symptoms, while the influenza virus can infect brain and leave central nervous system sequelae. As children are more vulnerable to infection, they are at risk of long-term neurological effects once their brains are infected. We previously demonstrated that functional changes in hippocampal neurons were observed in mice recovered from neonatal influenza infection. In this study, we investigated changes in myelination properties that could affect neural dysfunction. Mice were infected with the influenza virus on postnatal day 5. Tissues were harvested from recovered mice 21-days post-infection. The expression levels for myelin basic protein (MBP) were determined, and immunohistochemical staining and transmission electron microscopy were performed. Real-time polymerase chain reaction and Western blot analyses showed that mRNA and protein expressions increased in the hippocampus and cerebellum of recovered mice. Increased MBP-staining signal was observed in the recovered mouse brain. By calculating the relative thickness of myelin sheath in relation to nerve fiber diameter (G-ratio) from electron photomicrographs, an increased G-ratio was observed in both the hippocampus and cerebellum of recovered mice. Influenza infection in oligodendrocyte-enriched primary brain cell cultures showed that proinflammatory cytokines may induce MBP upregulation. These results suggested that increased MBP expression could be a compensatory change related to hypomyelination, which may underlie neural dysfunction in recovered mice. In summary, the present results demonstrate that influenza infection during the neonatal period affects myelination and further induces functional changes in influenza-recovered mouse brain.

Multiple Age-Associated Mitochondrial DNA Deletions in Mouse Brain

  • Kim, Jin-Sun;Kim, Min-Jung;Kwon, In-Sook;Song, Eun-Sook
    • BMB Reports
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    • v.30 no.1
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    • pp.33-36
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    • 1997
  • Age-dependent deletion of mitochondrial DNA (mtDNA) was detected in mouse brain using PCR method. The size of the deleted fragment was 0.5 kb, 0.9 kb. 1.7 kb and 4.3 kb in the region between cytochrome b gene and ATPase 6 gene. The deleted fragment was increased gradually from 3-month to 22month Direct repeat sequence flanking the deletion in 0.5 kb PCR product was TAAT.

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A Blood-brain Barrier Permeable Derivative of 5-Fluorouracil: Preparation, Intracellular Localization, and Mouse Tissue Distribution

  • Im, Jung-Kyun;Biswas, Goutam;Kim, Wan-Il;Kim, Kyong-Tai;Chung, Sung-Kee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.3
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    • pp.873-879
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    • 2011
  • 5-Fluorouracil (5-FU), an anticancer agent was covalently attached to the recently developed sorbitol-based G8 transporter, and the conjugate (7) with FITC was found to have an affinity toward mitochondria and to readily cross BBB to gain an entry into mouse brain. Measured by $IC_{50}$, the conjugate (9) without the fluorophore showed enhanced cytotoxic activity toward two types of multidrug-resistant cell lines. These results strongly suggest that the sorbitol-based G8 transporter can be utilized as a good CNS delivery vector.

Phenotypic Characterization of MPS IIIA (Sgshmps3a/ Sgshmps3a) Mouse Model

  • Park, Sung Won;Ko, Ara;Jin, Dong-kyu
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.4 no.1
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    • pp.26-36
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    • 2018
  • Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and CNS degeneration. Characterization of animal model is the beginning point of the therapeutic clinical trial. Mouse model has a limitation in that it is not a human and does not have all of the disease phenotypes. Therefore, delineate of the phenotypic characteristics of MPS IIIA mouse model prerequisite for the enzyme replace treatment for the diseases. We designed 6-month duration of phenotypic characterization of MPS IIIA mouse biochemically, behaviorally and histologically. We compared height and weight of MPS IIIA mouse with wild type from 4 weeks to 6 months in both male and female. At 6 months, we measured GAG storage in urine kidney, heart, liver, lung and spleen. The brain GAG storage is presented with Alcian blue staining, immunohistochemistry, and electron-microscopy. The neurologic phenotype is evaluated by brain MRI and behavioral study including open field test, fear conditioning, T-maze test and Y-maze test. Especially behavioral tests were done serially at 4month and 6month. This study will show the result of the MPS IIIA mouse model phenotypic characterization. The MPS IIIA mouse provides an excellent model for evaluating pathogenic mechanisms of disease and for testing treatment strategies, including enzyme or cell replacement and gene therapy.

Neuroprotective Effects of Hyangsayangwi-tang in MPTP-induced Mouse Model of Parkinson's Disease (MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)로 유도된 Parkinson's Disease 동물 모델을 이용한 향사양위탕의 신경 세포 보호 효과)

  • Go, Ga-Yeon;Kim, Yun-Hee;Ahn, Taek-Won
    • Journal of Sasang Constitutional Medicine
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    • v.26 no.2
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    • pp.165-179
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    • 2014
  • Objectives To evaluate the neuroprotective effects of Hyangsayangwi-tang (HY), a Korean traditional medicinal prescription in a Parkinson's disease mouse model. Methods Four groups(each of 10 mouse per group) were used in this study. The neuroprotective effect of HY was examined in a Parkinson's disease mouse model. C57BL/6 mouse treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30mg/kg/day), intraperitoneal (i.p.) for 5 days. Slow behavioral responses and memory disorder is the major clinical symptoms of PD. In order to investigate the effect of HY on recovery of behavioral deficits and memory, we examined the motor function and memory by using Morris water maze and Forced swimming test. Ischemic mouse brain stained with TTC(2,3,5 triphenyl tetrazolium chloride) in the MPTP-induced Parkinson's disease to find out ischemia and tissue damage in mouse. The convenient, simple, and accurate high-performance liquid chromatography (HPLC) method was established for simultaneous determination of neurotransmitters in MPTP-HY group. To measure the amount of dopamine in mice brain, striatum-substantia nigra, was examined by Bradford assay. Immunohistochemistry was examined in the MPTP-induced Parkinson's disease (PD) mouse to evaluate the neuroprotective effects of Hyangsayangwi-tang on hippocampal lesion, ST and SNpc. Results and Conclusions Hyangsayangwi-tang (HY) prevents MPTP-induced loss of serotonin, hippocampus and TH-ir cell.

Optimal Echo phase of FLASH sequence for Brain Enhancement scan of mouse at 9.4T MRI system (9.4T MRI FLASH Sequence에서 마우스의 뇌 조영증강 검사를 위한 적정 Echo phase)

  • Jeong, Hyunkeun;Kim, Mingi;Nam, Kichang;Jung, Hyundo;Ahn, Chigwon;Kim, Hochul
    • Journal of the Institute of Electronics and Information Engineers
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    • v.54 no.7
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    • pp.115-124
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    • 2017
  • The objective of study was to investigate the optimal echo phase for mouse brain enhancement scan using fast low angle shot (FLASH) sequence of 9.4T magnetic resonance imaging (MRI). For quantification based on this method, an MR phantom experiment and clinical research were done. The phantom experiment was conducted by fabricating three phantoms with different molar concentration of gadolinium to create changes in echo phase of 9.4T FLASH sequence used in mouse brain scans. In the phantom experiment, SSI was 25~27 [arbitrary units, a.u.] in each of 33 phases from $6{\pi}$ to $28{\pi}$, while RSP was 30~100 mmol. MPSI was 47~52 [a.u], while MPP, where MPSI is seen, was 0.8~9 mmol. EPMS was 80.8~108.0%, while ASIMP was formed between 21.1 and 31.8 [a.u]. In the clinical research, Finally, the occurrence rate of artifact that expressed -1 nd +1. The present study was able to quantify the degree of enhancement at FLASH sequence of 9.4T MRI, as well as identify the optimal echo phase during mouse brain enhancement scan.

Comparative study on Hsp25 expression in Mongolian gerbil and mouse cerebellum

  • Lee, Heang-Yeon;Kim, Seong-Hwan;Lee, Jae-Bong;Shin, Chang-Ho
    • Korean Journal of Veterinary Service
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    • v.29 no.4
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    • pp.469-482
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    • 2006
  • The term 'heat shock protein (Hsps)' was derived from the fact that these proteins were initially discovered to be induced by hyperthermic conditions. In response to a range of stressful stimuli, including hyperthermia, immobilization, UV radiation, amino acid analogues, arsenite, various chemicals, and drugs the mammalian brain demonstrates a rapid and intense induction of the heat shock protein. Moreover, Hsps were expressed on the various pathological conditions including trauma, focal or global ischemia, hypoxia, infarction, infections, starvation, and anoxia. Especially, Hsp25 has a protective activity, facilitated by the ability of the protein to decrease the intracellular levels of reactive oxygen species (ROS) as well as its chaperone activity, which favors the degradation of oxidized proteins. Recently, it has clearly demonstrated that Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal bands of purkinje cells in three distinct regions, the central zone (lobule VI-VII) and nodular zone (lobule IX-X), and paraflocculus. The Mongolian gerbil has been introduced into stroke study model because of its unique brain vasculature. There are no significant connections between the basilarvertebral system and the carotid system. This anatomy feature renders the mongolian gerbil susceptible to forebrain ischemia-induced seizure. The present study is designed to examine the pattern of Hsp25 expression in the cerebellum of this animal in comparison with that in mouse.