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Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function
Won, Hyejung,Lee, Hye-Ryeon,Gee, Heon Yung,Mah, Won,Kim, Jae-Ick,Lee, Jiseok,Ha, Seungmin,Chung, Changuk,Jung, Eun Suk,Cho, Yi Sul,Park, Sae-Geun,Lee, Jung-Soo,Lee, Kyungmin,Kim, Daesoo,Bae, Yong Chul Nature Publishing Group, a division of Macmillan P 2012 Nature Vol.486 No.7402
Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disablility. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2<SUP>??/??</SUP>) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-d-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with d-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2<SUP>??/??</SUP> mice. Furthermore, treatment of Shank2<SUP>??/??</SUP> mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2<SUP>??/??</SUP> mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.
Ha, Mina,Ju, Young-Su,Lee, Won Jin,Hwang, Seung-sik,Yoo, Sang-Chul,Choi, Kyung-Hwa,Burm, Eunae,Lee, Jieon,Lee, Yun-Keun,Im, Sanghyuk KOREAN ACADEMY OF MEDICAL SCIENCE 2018 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.33 No.9
<P><B>Background</B></P><P>In 2011, two roads in a residential area in Seoul were found to be contaminated with the radionuclide cesium-137 (<SUP>137</SUP>Cs). In response to public concerns, an epidemiological study was conducted.</P><P><B>Methods</B></P><P>The standardized cancer incidence ratios in the affected and neighboring regions were calculated based on the central cancer registry. Households in the region were sampled using the random stratified sampling technique, and questionnaires were administered to family members, via home visit and via students in elementary to high schools. Information on duration of residency and frequency of use of the roads was applied to calculate cumulative radiation exposure dose from the roads, alongside with the reported <SUP>137</SUP>Cs contamination amounts. Information on past medical history, perceived risk, anxiety and psychological stress was also obtained. Of the 31,053 residents, 8,875 were analyzed. To examine possible associations between radiation exposure and health problems, logistic regression adjusted for covariates were performed with consideration of the sampling design, population weight and stratification.</P><P><B>Results</B></P><P>No significant association was found between self-informed diseases, including cancers, and estimated radiation exposure dose. According to an increase of radiation level, a significant increase in anxiety in all and a decline in the psychosocial wellbeing of the adults was noted. The risk perception level was higher in the elderly, females, the less educated, and the highest exposed individuals.</P><P><B>Conclusion</B></P><P>This study provides a basis for risk communication with residents and community environmental health policy.</P>
Changes of Renal Peripheral Benzodiazepine Receptor in the Stress/Anxiety Response
Ha, Jeoung-Hee,Lee, Kwang-Hun,Cheung, Seung-Douk,Park, Hyung-Bae,Lee, Maan-Gee,Choi, Hyoung-Chul,Sohn, Uy-Dong,Lee, Kwang-Youn,Kim, Won-Joon The Korean Society of Pharmacology 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.5
Peripheral benzodiazepine receptor(PBR) has been indentified in various peripheral tissues including kidney. The physiological and pharmacological functions of PBR are still uncertain, althought it has been suggested that these are associated with the regulation of stress/anxiety response. Diazepam progeny, which were exposed to diazepam perinatally, was reported to be an animal model of chronic anxiety. However, PBR in the diazepam progenies are not known yet. In the present study, therefore, we examined the changes of PBR in the stress/anxiety response. Dams of rats were given injection of diazepam or vehicle during puerperium. Diazepam progenies showed increased level of anxiety on the performance of elevated plus maze, and increased Bmax of PBR. Saturation experiments followed by scatchard analysis of the results showed that the increase in the density of PBR and the affinity of the PBR remained unchanged. Forced swim stress increased anxiety on the plus maze in both groups of rats. In contrast to control, diazepam progenies did not show further upregulation of renal PBR immediately after swimming stress, but still higher than control. From the above results, it may be concluded that upregulation of renal PBR is associated with chronic anxiety as well as stress-induced response.
Ha, Dae Chul,Lee, Ha Young,Son, Yeo Won,Yuk, Soon Hong,Choi, Youn Woong,Kwak, Byung Kook,Shin, Byung Cheol,Cho, Cheong-Weon,Cho, Sun Hang Springer 2014 NANOSCALE RESEARCH LETTERS Vol.9 No.1
<P>The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)–C<SUB>16</SUB>-iron oxide (PHEA-C<SUB>16</SUB>-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C<SUB>16</SUB>-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C<SUB>16</SUB>-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution. The size of the nanoparticles was controlled by the amount of C<SUB>16</SUB>. The 3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after intravenous administration of PHEA-C<SUB>16</SUB>-iron oxide with the size of 20 nm. The <I>in vitro</I> and <I>in vivo</I> toxicity tests revealed the high biocompatibility of PHEA-C<SUB>16</SUB>-iron oxide nanoparticles. Therefore, PHEA-C<SUB>16</SUB>-iron oxide nanoparticles with 20-nm size can be potentially useful as T2-weighted MR imaging contrast agents for the detection of lymph nodes.</P>
Molecular Mimicry-Based Repositioning of Nutlin-3 to Anti-Apoptotic Bcl-2 Family Proteins
Ha, Ji-Hyang,Won, Eun-Young,Shin, Jae-Sun,Jang, Mi,Ryu, Kyoung-Seok,Bae, Kwang-Hee,Park, Sung Goo,Park, Byoung Chul,Yoon, Ho Sup,Chi, Seung-Wook American Chemical Society 2011 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.133 No.5