Proceedings for Annual Meeting of The Japanese Pharmacological Society最新文献_第9页

Mitochondria as a target of antivirals 线粒体作为抗病毒药物的靶标

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_3-b-s31-3

J. Yasuda

引用次数: 0

Points to consider in pre-clinical safety assessment of new modalities 新模式临床前安全性评估需要考虑的要点

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_3-b-s26-4

Kotaro Tamura

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KPR-5714, a novel TRPM8 antagonist, improves frequent urination in a model with enhanced bladder afferent nerve activity KPR-5714是一种新型TRPM8拮抗剂，在膀胱传入神经活动增强的模型中改善尿频

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_3-b-p-188

Shinjiro Watanabe, Akane Matsuzawa, Jun-ichi Kobayashi, Yoshikazu Fujimori

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In vivo imaging techniques to evaluate fatty liver in a diet-induced NAFLD model using PXB mice 使用PXB小鼠评估饮食诱导的NAFLD模型中脂肪肝的体内成像技术

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_3-b-p-248

Yasuhiro Horimoto, Ryutaro Nishikata, Y. Sasaki, K. Hayashida, Yosuke Numata, H. Tsusaki

引用次数: 0

Effect of intravenously administered adeno-associated virus encoding TrkB gene on hippocampal neurogenesis 静脉注射编码TrkB基因的腺相关病毒对海马神经发生的影响

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.95.0_2-yia-53

Yamashita Reiya, Takahiro Ishimoto, Y. Masuo, Y. Kato

{"title":"Effect of intravenously administered adeno-associated virus encoding TrkB gene on hippocampal neurogenesis","authors":"Yamashita Reiya, Takahiro Ishimoto, Y. Masuo, Y. Kato","doi":"10.1254/jpssuppl.95.0_2-yia-53","DOIUrl":"https://doi.org/10.1254/jpssuppl.95.0_2-yia-53","url":null,"abstract":"Hippocampal neurogenesis mediated by activation of tropomyosin receptor kinases B (TrkB) is thought to play important roles in repair of brain function injury caused by neurodegenerative disorders. Therefore, stimulation of TrkB-mediated neurogenesis would be a possible therapeutic target. In the present study, we examined effect of overexpression of TrkB gene in the brain on hippocampal neurogenesis and any behavior change invivo after systemic gene transduction with an aim to clarify possible treatment strategy. For such purpose blood-brain barrier permeable adeno-associated virus serotype PHP.eB (AAV-PHP.eB) was used to transduce TrkB gene in the brain. Flag-tagged mouse TrkB gene was first inserted to pAAV-CMV vector, followed by co-transfection with AAV-PHP. eB vector to construct the final AAV construct (AAV-PHP.eB-mTrkB-flag). Transfection with the transgene plasmid in neuroblastoma cell line Neuro2a increased expression of TrkB gene product, the phosphorylation of which was increased in the presence of a TrkB agonist 7,8-dihydroxyflavone, confirming activation of exogenously transfected TrkB. Intravenous administration of AAV-PHP.eB-mTrkB-flag not only increased expression of TrkB, but also tended to increase area of new-born neuron marker Dcx-positive cells in hippocampus compared to control AAV-treated mice, implying possible promotion of neurogenesis. Thus, AAV-mediated TrkB gene transduction would be the possible treatment of neurodegenerative disorders by performing further analyses of its pharmacological actions.","PeriodicalId":20464,"journal":{"name":"Proceedings for Annual Meeting of The Japanese Pharmacological Society","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86811393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cognitive dysfunction and hippocampal synaptic impairment induced by methamphetamine locally injection into the nucleus accumbens 伏隔核局部注射甲基苯丙胺致认知功能障碍和海马突触损伤

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.95.0_3-p-215

Tokuhara Reika, Naotaka Izuo, Yuka Kusui, Takashi Asano, A. Nitta

{"title":"Cognitive dysfunction and hippocampal synaptic impairment induced by methamphetamine locally injection into the nucleus accumbens","authors":"Tokuhara Reika, Naotaka Izuo, Yuka Kusui, Takashi Asano, A. Nitta","doi":"10.1254/jpssuppl.95.0_3-p-215","DOIUrl":"https://doi.org/10.1254/jpssuppl.95.0_3-p-215","url":null,"abstract":"[Introduction] Methamphetamine (METH) is one of the most widely addictive drugs in the world. Repeated drug use frequently leads to cognitive impairment, but no effective treatment has been established. In the presents study, we examined the cognitive function of mice with injection of METH to the nucleus accumbens (NAc) to clarify the mechanism of cognitive impairment induced by METH. [Method] C57BL/6J mice (8-week-old, male) received administration of METH viaimplanted cannula in the NAc for seven consecutive days. Behavioral experiments were performed to evaluate cognitive functions. To examine long-term potentiation (LTP), excitatory postsynaptic potential on Schaffer collateral in response to theta burst stimulation on CA1 was recorded on the acute hippocampal slices. Behavioral and electrophysiological experiments were performed one day after the last injection. Slices after stimulation were applied to Western blotto analyze phosphorylation of AMPA receptor (Ser831, Ser845). [Results] Mice with METH in the NAc showed cognitive impairment in the novel object recognition test. LTP and phosphorylation of AMPA receptors were reduced in mice treated with METH. [Conclusion] Local METH administration in the NAc is suggested to suppress hippocampal synaptic transmission to cause cognitive dysfunction.","PeriodicalId":20464,"journal":{"name":"Proceedings for Annual Meeting of The Japanese Pharmacological Society","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87051265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of molecular mechanism underlying cell death induced by an ALS/FTD-causative gene CHCHD10 ALS/ ftd致病基因CHCHD10诱导细胞死亡的分子机制分析

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.95.0_3-o-115

S. Kusakari, Yuri Kobayashi, Hiroaki Suzuki, M. Matsuoka

{"title":"Analysis of molecular mechanism underlying cell death induced by an ALS/FTD-causative gene CHCHD10","authors":"S. Kusakari, Yuri Kobayashi, Hiroaki Suzuki, M. Matsuoka","doi":"10.1254/jpssuppl.95.0_3-o-115","DOIUrl":"https://doi.org/10.1254/jpssuppl.95.0_3-o-115","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) is a motor neuron-specific degenerative disease, and frontotemporal dementia (FTD) is another neurodegenerative disease that causes atrophy of the frontal and temporal lobes. There are pathological and genetical overlap between ALS and FTD regarding their causative genes and the presence of ubiquitin- and TDP-43-positive inclusion bodies. However, the pathogenesis of ALS and FTD remains insufficiently characterized. CHCHD10 (C10), a familial ALS/FTD-causative gene, is expressed in mitochondria and is thought to be involved in the regulation of mitochondrial functions, although the mechanism underlying the C10 mutation-mediated onset of ALS/FTLD remains unknown. In this study, we generated C10-expressing adenoviruses to unravel the mechanism underlying cell death caused by C10 mutations. The results showed that overexpression of wild-type C10 or a C10 mutant induced cell death in parallel with increase in the transcription factor C/EBP homologous protein (CHOP) expression, the indicator of mitochondrial unfolded protein response. Importantly, the overexpression of the C10 mutant caused higher-level cell death and expression of CHOP than wild-type C10. These results suggest that the familial ALS/FTLD-linked mutation of C10 enhances motor neuron toxicity possibly by exaggerated mitochondrial stress.","PeriodicalId":20464,"journal":{"name":"Proceedings for Annual Meeting of The Japanese Pharmacological Society","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87108536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro and in vivo assessment of drug metabolism and hepatotoxicity using chimeric mice with humanized liver 人源化肝脏嵌合小鼠体外和体内药物代谢及肝毒性评价

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.95.0_2-s21-3

S. Sanoh

{"title":"In vitro and in vivo assessment of drug metabolism and hepatotoxicity using chimeric mice with humanized liver","authors":"S. Sanoh","doi":"10.1254/jpssuppl.95.0_2-s21-3","DOIUrl":"https://doi.org/10.1254/jpssuppl.95.0_2-s21-3","url":null,"abstract":"Unexpected hepatotoxicity is a major obstacle to drug development, frequently underlying discontinuation of drug development and withdrawal from the market. Drug metabolism and pharmacokinetics are often involved in hepatotoxicity. Therefore, it is necessary to establish invitroand invivomodels for predicting drug metabolism and related cases of hepatotoxicity. We focused on chimeric mice with humanized liver, consisting predominantly of human hepatocytes. Various human genes, encoding drug-metabolizing enzymes and transporters, are expressed in the liver. These chimeric mice were found to be useful for qualitative and quantitative prediction of human metabolite formation, pharmacokinetics, and drug-drug interactions. They are also useful for predicting hepatotoxicities, such as cholestasis and steatosis. Moreover, fresh hepatocytes isolated from the chimeric mice are useful for in vitro screening. It is possible to compare invitroand invivoprofiles of the same chimeric mice. One possible drawback could be the contribution of residual mouse hepatocytes and extrahepatic tissues, which may detract from predictability. Recently, novel improved models which overcome these problems have been developed, and increased prediction accuracy is expected.","PeriodicalId":20464,"journal":{"name":"Proceedings for Annual Meeting of The Japanese Pharmacological Society","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88198556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alteration of stress granule formation and clearance by S-Nitrosylation modification of G3BP1 s -亚硝基化修饰G3BP1对应力颗粒形成和清除的影响

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_2-b-p-088

Nodoka Ito, Kana Fujikawa, Takashi Uehara

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Effectiveness of proton pump inhibitors on obsessive-compulsive disease discovered in real-world data and the molecular mechanism 质子泵抑制剂对强迫症的有效性在现实世界数据和分子机制中发现

Proceedings for Annual Meeting of The Japanese Pharmacological Society Pub Date : 2022-01-01 DOI: 10.1254/jpssuppl.96.0_3-b-hs04-4

Hikari Hatakama, Nozomi Asaoka, K. Nagayasu, H. Shirakawa, Shuji Kaneko

引用次数: 0