A5084457844- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Phagocytosis and Immune Regulation
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Signaling Pathways in Disease
- Biochemical and Structural Characterization
- RNA Interference and Gene Delivery
- Neuropeptides and Animal Physiology
- Genetics and Neurodevelopmental Disorders
- Protein Tyrosine Phosphatases
- Receptor Mechanisms and Signaling
- Memory and Neural Mechanisms
- Peptidase Inhibition and Analysis
- Stress Responses and Cortisol
- RNA regulation and disease
- Neurotransmitter Receptor Influence on Behavior
- Pancreatic function and diabetes
- bioluminescence and chemiluminescence research
- Treatment of Major Depression
- Genetic Associations and Epidemiology
- Cognitive Abilities and Testing
Fujita Health University
2011-2022
Fujita Health University Hospital
2019
National Institute of Advanced Industrial Science and Technology
2004-2018
Japan Society for the Promotion of Science
2017-2018
Japan Science and Technology Agency
2011-2016
National Institutes of Health
2008-2012
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2009-2012
Protein Research Foundation
2002-2004
Osaka University
2001-2004
Nara Institute of Science and Technology
2001
Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation TrkB-FL was blocked by Trk inhibitors, suggesting a tyrosine kinase translocation. Disruption depleting cholesterol cell surface ligand-induced Moreover, disruption prevented...
Abstract Background Proneurotrophins and mature neurotrophins elicit opposite effects via the p75 neurotrophin receptor (p75 NTR ) Trk tyrosine kinase receptors, respectively; however molecular roles of proneurotrophins in CNS are not fully understood. Results Based on two rare single nucleotide polymorphisms (SNPs) human brain-derived neurotrophic factor (BDNF) gene, we generated R125M-, R127L- R125M/R127L-BDNF, which have amino acid substitution(s) near cleavage site between pro-...
Brain-derived neurotrophic factor (BDNF) exerts multiple biological functions in the CNS. Although BDNF can control transcription and protein synthesis, it still remains open to question whether regulates lipid biosynthesis. Here we show that elicits cholesterol biosynthesis cultured cortical hippocampal neurons. Importantly, elicited synthesis neurons, but not glial cells. Quantitative reverse transcriptase-PCR revealed stimulated of enzymes biosynthetic pathway. BDNF-induced increases were...
Schnurri-2 (Shn-2), an nuclear factor-κB site-binding protein, tightly binds to the enhancers of major histocompatibility complex class I genes and inflammatory cytokines, which have been shown harbor common variant single-nucleotide polymorphisms associated with schizophrenia. Although related immunity are implicated in schizophrenia, there has no study showing that their mutation or knockout (KO) results Here, we show Shn-2 KO mice behavioral abnormalities resemble those schizophrenics....
Abstract Background In the central nervous system (CNS), muscarinic plays key roles in learning and memory, as well regulation of many sensory, motor, autonomic processes, is thought to be involved pathophysiology several major diseases CNS, such Alzheimer's disease, depression, schizophrenia. Previous studies reveal that M 4 receptor knockout (M R KO) mice displayed an increase basal locomotor activity, sensitivity prepulse inhibition (PPI)-disrupting effect psychotomimetics, normal PPI....
Abstract Molecules that govern the formation, integrity, and function of hippocampus remain an important area investigation. Here we show absence proneuropeptide processing enzyme, carboxypeptidase E (CPE) in CPE knock‐out (KO) mice had a profound effect on memory, synaptic physiology, cytoarchitecture these animals. Adult CPE‐KO displayed deficits memory consolidation as revealed by water‐maze, object preference, social transmission food preference tests. These also showed no evoked...
Previously we demonstrated that chromogranin A (CgA) promoted secretory granule biogenesis in endocrine cells by stabilizing and preventing protein degradation the Golgi, through up-regulation of expression protease inhibitor, nexin-1 (PN-1). However, mechanism which CgA signals increase PN-1 is unknown. Here identified a 2.9-kDa CgA-C-terminus peptide, named serpinin, conditioned media from AtT-20 cells, corticotroph cell line, up-regulated mRNA expression. Serpinin was secreted upon high...
Three forms of serpinin peptides, (Ala26Leu), pyroglutaminated (pGlu)-serpinin (pGlu23Leu), and serpinin-Arg-Arg-Gly (Ala29Gly), are derived from cleavage at pairs basic residues in the highly conserved C terminus chromogranin A (CgA). Serpinin induces PN-1 expression neuroendocrine cells to up-regulate granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while pGlu-serpinin inhibits cell death. The aim this study was test hypothesis that peptides produced heart act as novel...
Abstract Carboxypeptidase E (CPE) is involved in maturation of neuropeptides and sorting brain‐derived neurotrophic factor (BDNF) to the regulated pathway for activity‐dependent secretion from CNS neurons. CPE knockout (CPE‐KO) mice have many neurological deficits, including deficits learning memory. Here, we analyzed dendritic arborization spine morphology CPE‐KO determine a possible correlation defects such structures with observed these animals. Analysis pyramidal neurons layer V cerebral...
Abstract Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. candidate susceptibility for neuropsychiatric disorders, including schizophrenia, bipolar disorder, attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined N -ethyl- -nitrosourea (ENU)-generated mutant mouse...
Cluster of differentiation 47 (CD47) is a member the immunoglobulin superfamily which functions as ligand for extracellular region signal regulatory protein α (SIRPα), abundantly expressed in brain. Previous studies, including ours, have demonstrated that both CD47 and SIRPα fulfill various central nervous system (CNS), such modulation synaptic transmission neuronal cell survival. We previously reported involved regulation depression-like behavior mice forced swim test through its tyrosine...
To investigate the roles of amino acid residues around chromophore in photoactive yellow protein (PYP), new mutants, Y42A, E46A, and T50A were prepared. Their spectroscopic properties compared with those wild-type, Y42F, E46Q, T50V, R52Q, E46Q/T50V, which previously prepared specified. The absorption maxima observed at 438, 469, 454 nm, respectively. results pH titration for demonstrated that PYP mutant, like was protonated bleached under acidic conditions. red-shifts mutants tended toward a...
Little is known about the role of integrin-associated protein (IAP, or CD47) in neuronal development and its function central nervous system. We investigated responses IAP-overexpressing cortical neurons using a virus-gene transfer found that dendritic outgrowth was significantly enhanced IAP (form 4)-transfected neurons. Furthermore, synaptic proteins including synaptotagmin, syntaxin, synapsin I, SNAP25 (25-kDa synaptosomal associated protein) were up-regulated. In accordance with this...
A tumor suppressor gene, Adenomatous polyposis coli (Apc), is expressed in the nervous system from embryonic to adulthood stage, and transmits Wnt signaling pathway which schizophrenia susceptibility genes, including T-cell factor 4 (TCF4) calcineurin (CN), are involved. However, functions of Apc largely unknown. In this study, as first evaluation function system, we have investigated behavioral significance applying a battery tests heterozygous knockout (Apc+/−) mice. Apc+/− mice showed no...
Abstract Aim The striatum, a main component of the basal ganglia, is critical part motor and reward systems brain. It consists GABAergic cholinergic neurons receives projections dopaminergic, glutamatergic, serotonergic from other brain regions. Brain‐derived neurotrophic factor (BDNF) plays multiple roles in central nervous system, striatal BDNF has been suggested to be involved psychiatric neurodegenerative disorders. However, transcriptomic impact on striatum remains largely unknown. In...
Abstract The death and survival of neuronal cells are regulated by various signaling pathways during development the brain in diseases. Previously, we demonstrated that adhesion molecule immunoglobulin‐like with tyrosine‐based activation motifs/SHP substrate 1 (BIT/SHPS‐1) is involved brain‐derived neurotrophic factor (BDNF)‐promoted cell survival. Here, report apoptosis‐inducing effect CD47/integrin‐associated protein (IAP), heterophilic binding partner BIT/SHPS‐1, on cells. We generated a...
Serpinins are a family of peptides derived from proteolytic cleavage the penultimate and last pair basic residues at C-terminus Chromogranin A. Three forms naturally occurring serpinin have been found in AtT-20 pituitary cells rat heart. They serpinin, pyrogutaminated (pGlu) -serpinin C-terminally extended form, serpinin-RRG. In addition pGlu-serpinin has brain, primarily neurites nerve terminals shown to protective effects against oxidative stress on neurons cells. Serpinin also...