Takeo Yoshikawa
A5067676082- Genetics and Neurodevelopmental Disorders
- Genetic Associations and Epidemiology
- Autism Spectrum Disorder Research
- Bipolar Disorder and Treatment
- Genomic variations and chromosomal abnormalities
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Peroxisome Proliferator-Activated Receptors
- Neurotransmitter Receptor Influence on Behavior
- Helicobacter pylori-related gastroenterology studies
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Congenital heart defects research
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Diet and metabolism studies
- Amino Acid Enzymes and Metabolism
- Genetic Syndromes and Imprinting
- Ion channel regulation and function
- Metabolism and Genetic Disorders
- RNA regulation and disease
- Tryptophan and brain disorders
- Nuclear Receptors and Signaling
- Phosphodiesterase function and regulation
RIKEN Center for Brain Science
2016-2025
Hokkaido University
1980-2023
Ochanomizu University
2020
Fujita Health University
2010-2018
Osaka University
1996-2018
RIKEN
2003-2018
Kanazawa University
2018
Kōchi University
2018
Tokushima University
2008-2018
Kyoto Prefectural University of Medicine
2006-2017
Bipolar disorder is a severe mental illness characterized by mood swings of elation and depression. Family, twin, adoption studies suggest complex genetic etiology that may involve multiple susceptibility genes an environmental component. To identify chromosomal loci contributing to vulnerability, we have conducted genome-wide scan on approximately 396 individuals from 22 multiplex pedigrees using 607 microsatellite markers. Multipoint nonparametric analysis detected the strongest evidence...
Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ 2,095 controls Japanese population confirmed an increased burden of rare exonic CNVs both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to disorders, were found about 8% which was significantly higher than controls. Phenotypic analysis revealed association...
Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In present GWAS (Phase I/II), which included 2964 61 887 control subjects from Japanese population, we detected a novel locus at 11q12.2 (rs28456, P=6.4 × 10−9), region known contain regulatory genes plasma lipid levels (FADS1/2/3). A subsequent meta-analysis...
Highlights•Exome sequencing of Japanese ASD trios supports "de novo paradigm"•Integrative analyses were conducted by combining with published DNM data•Integrative confirm and extend ASD-related molecular brain networks•Integrative identify 61 significant genes as well drug candidatesSummaryRecent studies have established important roles de mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs 262 probands origin the paradigm" ASDs across ethnicities. Based on this...
The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin rats were investigated. total area erosions concentration peroxides mucosa increased time after administration (20 mg/kg, orally). alpha-tocopherol:total cholesterol ratio serum was significantly decreased activity glutathione peroxidase, an important enzyme to scavenger peroxides, inhibited indomethacin. Treatments superoxide dismutase...
Downregulation of oligodendrocyte-related genes, referred to as oligodendrocyte dysfunction, in schizophrenia has been revealed by DNA microarray studies. Because oligodendrocyte-specific transcription factors regulate the differentiation oligodendrocytes, genes encoding them are prime candidates for dysfunction schizophrenia. We found that cytosine-guanine dinucleotide (CpG) island sex-determining region Y-box containing gene 10 (SOX10), an factor, tended be highly methylated brains...
Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals show high PPI with C3H/He (C3) low PPI. We detected six major acoustic startle response, and four latency to response peak, some of which were sex-dependent. A promising candidate Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), gene...
Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, its underlying molecular mechanisms remain unknown. Ca(2+)-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates exocytosis of dense-core vesicles, human CADPS2 located within autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor...
<h3>Context</h3> Various factors are involved in the pathogenesis of schizophrenia. Accumulation advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase reactive compounds (RCOs) and their attendant protein modifications. Vitamin B<sub>6</sub>is known to detoxify RCOs, products. Glyoxalase I (GLO1) is one enzymes required for cellular detoxification RCOs. <h3>Objectives</h3> To examine whether plasma levels pentosidine serum vitamin...
The calcineurin cascade is central to neuronal signal transduction, and genes in this network are intriguing candidate schizophrenia susceptibility genes. To replicate extend our previously reported association between the PPP3CC gene, encoding catalytic γ-subunit, schizophrenia, we examined 84 SNPs from 14 calcineurin-related for genetic by using 124 Japanese schizophrenic pedigrees. Four of these ( , EGR2 EGR3 EGR4 ) showed nominally significant with schizophrenia. In a postmortem brain...
For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium effectively augment antidepressant drugs treatment of refractory major depressive episodes prevent relapses recurrent unipolar depression. In contrast many psychiatric drugs, outlasted various...
Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most the previous studies have restricted biomarkers energy metabolism, while most genetic based on mutations mitochondrial DNA (mtDNA). Despite mtDNA, proteins essential for replication and function are encoded by genomic DNA; so far, there very few those...
Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes (b) examine shared risk of across (East Asian [EAS] European [EUR]) populations and/or trans-diseases (SCZ, bipolar [BD], major depressive [MDD]) within EAS between EUR...
New neurons are continually produced after birth from neural stem/progenitor cells (NSCs/NPCs) in the hippocampal dentate gyrus (DG). Recent studies have reported that fatty acid binding protein 7 (Fabp7/brain lipid (BLBP)) is required for maintenance of embryonic NSCs/NPCs and identified an association between Fabp7 gene behavioral paradigms correlate with functions. However, specific roles Fabps postnatal neurogenesis remain unknown. Herein, we demonstrate effects Fabp7, another Fabp,...
Autism spectrum disorder is a heterogeneous neurodevelopmental with strong genetic basis. To identify common variations conferring the risk of ASD, we performed two‐stage genome‐wide association study using ASD family and healthy control samples obtained from East Asian populations. A total 166 families ( n = 500) 642 controls Japanese population were used as discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) genotyped Affymetrix Genome‐Wide Human SNP array 6.0...
Although evidence for mitochondrial dysfunction in the pathogenesis of bipolar disorder (BD) has been reported, precise biological basis remains unknown, hampering search novel biomarkers. In this study, we performed metabolomics cerebrospinal fluid (CSF) from male BD patients (n=54) and age-matched healthy controls (n=40). Subsequently, post-mortem brain analyses, genetic CSF samples rats treated with lithium or valproic acid were also performed. After multivariate logistic regression,...
Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and mature brains is involved uptake transportation of fatty acids, signal transduction, gene transcription. Fabp7 knockout ( KO) mice show behavioral phenotypes reminiscent human neuropsychiatric disorders such as schizophrenia. However, direct evidence showing how FABP7 deficiency leads to altered brain function lacking. Here, we examined neuronal dendritic morphology synaptic plasticity medial prefrontal cortex...