A5102859713- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Melanoma and MAPK Pathways
- Synthesis of Tetrazole Derivatives
- Synthesis and biological activity
- Pluripotent Stem Cells Research
- 3D Printing in Biomedical Research
- Cutaneous Melanoma Detection and Management
- Epilepsy research and treatment
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Sleep and Wakefulness Research
- Cell Image Analysis Techniques
- Neuropeptides and Animal Physiology
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Click Chemistry and Applications
- Regulation of Appetite and Obesity
- Virus-based gene therapy research
- Electrochemical Analysis and Applications
- Analog and Mixed-Signal Circuit Design
- RNA regulation and disease
- Pregnancy-related medical research
Eisai (Japan)
2013-2025
University of Tsukuba
1990-2025
Health and Environmental Sciences Institute
2019
Asahi Kasei (Japan)
2019
Japan Medical Association
2015-2017
Shimane University
2014
Howard Hughes Medical Institute
2003-2004
Japan Science and Technology Agency
2004
The University of Texas Southwestern Medical Center
2003-2004
Science and Technology Corporation (United States)
2003
Leptin is an adipose-derived hormone that regulates a wide variety of physiological processes, including feeding behavior, metabolic rate, sympathetic nerve activity, reproduction, and immune response. Circulating leptin levels are tightly regulated according to energy homeostasis in vivo. Although mechanisms for the regulation production adipocytes not well understood, G protein-coupled receptors may play important role this adipocyte function. Here we report C2-C6 short-chain fatty acids,...
ABSTRACT The homeobox gene Emx2 is a mouse homologue of Drosophila head gap empty spiracles (ems) and essential for the development dorsal telencephalon (Yoshida, M., Suda, Y., Matsuo, I., Miyamoto, N., Takeda, Kuratani, S. Aizawa, (1997)Development 124, 101-111). At same time, expressed in epithelial components developing urogenital system and, mutant mice, kidneys, ureters, gonads genital tracts were completely missing. Pax-2 c-ret expressions Wolffian duct WT-1 GDNF metanephric blastema...
ABSTRACT The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty spiracles, their expression patterns have suggested involvement in regional patterning the forebrain. To define functions we introduced mutations into these loci. newborn mutants displayed defects archipallium structures that believed to play essential roles learning, memory behavior: dentate gyrus was missing, hippocampus medial limbic cortex were greatly reduced size. In contrast, subtle adult mutant...
GPR7 and GPR8 are orphan G protein-coupled receptors that highly similar to each other. These expressed predominantly in brain, suggesting roles central nervous system function. We have purified an endogenous peptide ligand for from bovine hypothalamus extracts. This peptide, termed neuropeptide B (NPB), has a C-6-brominated tryptophan residue at the N terminus. It binds activates human or with median effective concentrations (EC 50 ) of 0.23 nM 15.8 nM, respectively. In situ hybridization...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are anticipated to be a useful tool for conducting proarrhythmia risk assessments of drug candidates. However, torsadogenic prediction paradigm using hiPSC-CMs has not yet been fully established.Extracellular field potentials (FPs) were recorded from the multi-electrode array (MEA) system. The effects on FPs evaluated with 60 drugs, including 57 various clinical risks. Actual concentrations in medium measured equilibrium...
Multi-electrode array (MEA) systems and human induced pluripotent stem (iPS) cell-derived cardiomyocytes are frequently used to characterize the electrophysiological effects of drug candidates for prediction QT prolongation proarrhythmic potential. However, optimal experimental conditions obtaining reliable data, such as high-pass filter (HPF) frequency cell plating density, remain be determined. Extracellular field potentials (FPs) were recorded from iPS cardiomyocyte sheets by using MED64...
ADAM22 is a member of the ADAM gene family, but fact that it expressed only in nervous systems makes unique. ADAM22's sequence similarity to other ADAMs suggests be an integrin binder and thus have role cell-cell or cell-matrix interactions. To elucidate physiological functions ADAM22, we employed targeting generate knockout mice.ADAM22-deficient mice were produced good accordance with Mendelian ratio appeared normal at birth. After one week, severe ataxia was observed, all homozygotes died...
The role of N-type Ca2+ channels in nociceptive transmission was examined genetically engineered mice lacking the α1B subunit and their heterozygote wild-type littermates. In α1B-deficient mice, channel activities dorsal root ganglion neurons spinal synaptoneurosomes were eliminated without compensation by other types voltage-dependent channels. showed a diminution phase 2 responses more extensively than 1 formalin test. exhibited significantly increased thermal thresholds hot plate test,...
N-type voltage-dependent Ca(2+) channels (VDCCs), predominantly localized in the nervous system, have been considered to play an essential role a variety of neuronal functions, including neurotransmitter release at sympathetic nerve terminals. As direct approach elucidating physiological significance VDCCs, we generated mice genetically deficient alpha(1B) subunit (Ca(v) 2.2). The alpha(1B)-deficient null mice, surprisingly, normal life span and are free from apparent behavioral defects. A...
The aims of this study were to (1) characterize basic electrophysiological elements human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond clinical properties such as QT-RR relationship, (2) determine the applicability QT correction and analysis methods, (3) if how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects Torsades de pointes (TdP). Field potential recordings obtained from commercially available hiPSC-CMs using...
Bolus-administered intracerebroventricular (ICV) relaxin-3 has been reported to increase feeding. In this study, examine the role of signaling in energy homeostasis, we studied effects chronically administered ICV on body weight gain and locomotor activity rats. Two groups animals received vehicle or at 600 pmol/head/day, delivered with Alzet osmotic minipumps. receiving relaxin-3, food consumption were statistically significantly higher than those group during 14-day infusion. During light...
Phosphodiesterase 9 (PDE9) plays a critical role in synaptic plasticity and cognitive function by modulating cyclic GMP (cGMP). Many reports have shown that PDE9 inhibition improves rodents. Several studies found the NO/cGMP/PKG pathway is downregulated patients with Alzheimer's disease (AD) or dementia Lewy bodies (DLB) older individuals. A inhibitor could therefore be potential therapeutic approach for improving dysfunction dementia, including AD DLB. We previously discovered novel...
Evaluation using beat propagation analysis of human iPS cardiomyocytes is an effective approach for assessing cardiac safety in drug development. However, current applications are primarily focused on detecting QT prolongation and arrhythmia risk, while its ability to comprehensively detect cardiotoxicity remains insufficient. Additionally, predicting the mechanism action, which crucial development, challenging. In this study, we employed field potential imaging (FPI) ultra-high-density...
Abstract Drug-induced convulsions/seizures are a serious adverse event in the clinic; however, precise convulsion/seizure risk assessment remains challenging, particularly early phase of drug development. There is demand for reliable vitro assay systems that can predict vivo convulsions. Here we investigated usefulness microelectrode array (MEA) assays using rat primary neurons by comparing them with an convulsion study fourteen reference drugs known to cause seizure/convulsion: paroxetine,...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are expected to become a useful tool for proarrhythmia risk prediction in the non-clinical drug development phase. Several features including electrophysiological properties, ion channel expression profile and responses were investigated using commercially available hiPSC-CMs, such as iCell-CMs Cor.4U-CMs. Although drug-induced arrhythmia has been extensively examined by microelectrode array (MEA) assays iCell-CMs, it not...
Differential properties of voltage-dependent Ca 2 + channels have been primarily ascribed to the α 1 subunit, which 10 different subtypes are currently known. For example, that conduct N-type current possess 1B subunit (Ca v 2.2), has localized, inter alia , piriform cortex, hippocampus, hypothalamus, locus coeruleus, dorsal raphe, thalamic nuclei, and granular layer cortex. Some these regions previously implicated in metabolic vigilance state control, selective block channel causes...
Many clinical cases of acquired resistance to the BRAF inhibitor vemurafenib have recently been reported. One causes this is downstream kinase point mutation MEK1-C121S. This confers not only vemurafenib, but also allosteric MEK selumetinib (AZD6244). Here, we investigated pharmacologic activities and effectiveness novel E6201 against (v-raf murine sarcoma viral oncogene homolog B1)-V600E mutant melanoma harboring MEK1-C121S mutation. A cell-free assay confirmed that an ATP-competitive...