A5001341469- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Virus-based gene therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Receptor Mechanisms and Signaling
- Photoreceptor and optogenetics research
- Traumatic Brain Injury and Neurovascular Disturbances
- RNA Interference and Gene Delivery
- Neuroscience of respiration and sleep
- Vestibular and auditory disorders
- Retinal Development and Disorders
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Memory and Neural Mechanisms
- Neuroscience and Neural Engineering
- Neuroendocrine regulation and behavior
- Crystallization and Solubility Studies
- Thermal Regulation in Medicine
- Immune Response and Inflammation
- X-ray Diffraction in Crystallography
- Amino Acid Enzymes and Metabolism
Gunma University
2016-2025
Niigata University
2023
Tohoku University
2010-2021
Institute of Molecular Medicine
2016
Krasnoyarsk State Medical University
2016
Nagaoka University
2014
Nagaoka University of Technology
2014
Shitennoji University
2014
Kanazawa University
2004-2012
Akita University
2010
NMDA receptors require both L-glutamate and the coagonist glycine for efficient channel activation. The binding site of these heteromeric receptor proteins is formed by regions NMDAR1 (NR1) subunit that display sequence similarity to bacterial amino acid proteins. Here, we demonstrate glutamate located on homologous NR2B subunit. Mutation residues within N-terminal domain loop region between membrane segments M3 M4 significantly reduced efficacy glutamate, but not glycine, in gating. Some...
Abstract Transcranical direct current stimulation (tDCS) is a treatment known to ameliorate various neurological conditions and enhance memory cognition in humans. tDCS has gained traction for its potential therapeutic value; however, little about mechanism of action. Using transgenic mouse expressing G-CaMP7 astrocytes subpopulation excitatory neurons, we find that induces large-amplitude astrocytic Ca 2+ surges across the entire cortex with no obvious changes local field potential....
Abstract Astrocytes may function as mediators of the impact noradrenaline on neuronal function. Activation glial α1-adrenergic receptors triggers rapid astrocytic Ca 2+ elevation and facilitates synaptic plasticity, while activation β-adrenergic elevates cAMP levels modulates memory consolidation. However, dynamics these processes in behaving mice remain unexplored, do interactions between distinct second messenger pathways. Here we simultaneously monitored demonstrate that messengers are...
Abstract : Phosphorylation of the glutamate receptor is an important mechanism synaptic plasticity. Here, we show that C terminus GluR2 α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) phosphorylated by protein kinase and serine‐880 major phosphorylation site. This also occurs in human embryonic kidney (HEK) cells addition 12‐ O ‐tetradecanoylphorbol 13‐acetate. Our immunoprecipitation experiment revealed drastically reduced affinity for receptor‐interacting (GRIP), a PDZ...
The N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors is a heterooligomeric membrane protein composed homologous subunits. Here, the contribution M3-M4 loop NR1 subunit to binding and co-agonist glycine was investigated by site-directed mutagenesis. Substitution phenylalanine residues at positions 735 or 736 produced 15- 30-fold reduction in apparent affinity without affecting competitive antagonist 7-chlorokynurenic acid; mutation both caused >100-fold decrease...
cAMP is a common second messenger that involved in various physiological processes. To expand the colour palette of available indicators, we developed red indicator named "Pink Flamindo" (Pink Fluorescent indicator). The fluorescence intensity Pink Flamindo increases 4.2-fold presence saturating dose cAMP, with excitation and emission peaks at 567 nm 590 nm, respectively. Live-cell imaging revealed effective for monitoring spatio-temporal dynamics intracellular generated by photoactivated...
Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family versatile cell recognition molecules, as retrograde signals for climbing fiber to Purkinje in developing mouse cerebellum. Knockdown Sema3A, secreted semaphorin, or its receptor fibers accelerated day 8 (P8) P18. Conversely, knockdown Sema7A, membrane-anchored...
Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in MJD1 gene. This expansion translates into polyglutamine tract that confers toxic gain-of-function to mutant protein--ataxin-3, leading neurodegeneration specific brain regions, with particular severity cerebellum. No treatment able modify progression available. However, gene silencing RNA interference has shown...
Compared with the knowledge of maternal care, much less is known about factors required for paternal parental care. Here we report that new sires laboratory mice, though not spontaneously parental, can be induced to show maternal-like care (pup retrieval) using signals from dams separated their pups. During this interaction, mates emit 38-kHz ultrasonic vocalizations male partners, which are equivalent occur following pheromone stimulation. Without these or in absence mates, do retrieve pups...
Machado-Joseph disease or spinocerebellar ataxia type 3, the most common dominantly-inherited ataxia, results from translation of polyglutamine-expanded and aggregation prone ataxin 3 protein. Clinical manifestations include cerebellar pyramidal signs there is no therapy to delay progression. Beclin 1, an autophagy-related protein essential gene for cell survival, decreased in several neurodegenerative disorders. This study aimed at evaluating if lentiviral-mediated beclin 1 overexpression...
Machado-Joseph disease is a neurodegenerative without effective treatment. Patients with exhibit significant motor impairments such as gait ataxia, associated multiple neuropathological changes including mutant ATXN3 inclusions, marked neuronal loss and atrophy of the cerebellum. Thus, an treatment symptomatic patients may require cell replacement, which we investigated in this study. For purpose, injected cerebellar neural stem cells into cerebellum adult transgenic mice assessed effect on...
Cerebellar Purkinje cells (PCs) express a large amount of the γ isoform protein kinase C (PKCγ) and modest level PKCα. The PKCγ is involved in pruning climbing fiber (CF) synapses from developing PCs, PKCα plays critical role long-term depression (LTD) at parallel (PF)-PC synapses. Moreover, PKC signaling PCs negatively modulates nonselective transient receptor potential cation channel type 3 (TRPC3), opening which elicits slow EPSCs PF-PC Autosomal dominant spinocerebellar ataxia 14 (SCA14)...
Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by gene defect, leading to movement disorder such as cerebellar ataxia. It remains largely unknown which functional defect contributes the ataxic phenotype in SCA1. In this study, we report dysfunction of metabotropic glutamate receptor (mGluR) signalling, leads smaller slow synaptic responses, reduced dendritic Ca2+ signals and impaired plasticity at synapses, early stage SCA1 model mice. We also show...
Adeno-associated virus (AAV) vectors have excellent properties as gene transfer vehicles. The recent development of AAV-PHP.eB, highly BBB-permeable capsid variant AAV serotype 9, has opened up systemic application for whole brain transduction. To attain high transduction efficacy, much efforts been paid to purify using gradient centrifugation or column chromatography. These methods are time-consuming, cost substantially and require expensive equipment.We propose a simple purification method...