A5019667159- Genetics and Neurodevelopmental Disorders
- Bipolar Disorder and Treatment
- Mitochondrial Function and Pathology
- Circadian rhythm and melatonin
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Endoplasmic Reticulum Stress and Disease
- Metabolism and Genetic Disorders
- Tryptophan and brain disorders
- Microbial metabolism and enzyme function
- Epigenetics and DNA Methylation
- Photoreceptor and optogenetics research
- Porphyrin Metabolism and Disorders
- GABA and Rice Research
- Biochemical Acid Research Studies
- Stress Responses and Cortisol
- Diet and metabolism studies
- Retinal Development and Disorders
- Genomics and Rare Diseases
- RNA Research and Splicing
- Cardiac electrophysiology and arrhythmias
- Spaceflight effects on biology
Carl von Ossietzky Universität Oldenburg
2023-2025
RIKEN Center for Brain Science
2014-2024
Kanazawa University
2024
RIKEN
2007-2009
Japan Science and Technology Agency
2002
The University of Tokyo
1997-2001
National Institute for Physiological Sciences
2001
Tokyo University of Science
1997
Melatonin is a pineal hormone produced at night; however, many strains of laboratory mice are deficient in melatonin. Strangely enough, the gene encoding HIOMT enzyme (also known as ASMT) that catalyzes last step melatonin synthesis still unidentified house mouse ( Mus musculus ) despite completion genome sequence. Here we report identification Hiomt gene, which was mapped to pseudoautosomal region (PAR) sex chromosomes. The highly polymorphic, and nonsynonymous SNPs were found...
Although inflammatory cytokines are established biomarkers of mood disorders, their molecular mechanism is not known. We hypothesized that circulating mitochondrial DNA (mtDNA) contributes to inflammation and could be used as biomarkers. investigated if mtDNA level associated with can a biomarker disorders. Plasma concentration was measured real-time quantitative PCR targeting two regions the plasma levels four (GM-CSF, IL-2, IL-4, IL-6) were multiplex immunoassay method in 109 patients...
Increased levels of lactate, an end-product glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These in lactate can result decreased brain pH, which has implicated patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed five mouse models schizophrenia, bipolar disorder, and autism, suggesting shared endophenotype among these disorders rather than mere artifacts due...
Accumulation of unfolded proteins in the endoplasmic reticulum initiates intracellular signaling termed protein response (UPR). Although Xbp1 serves as a pivotal transcription factor for UPR, physiological role UPR and central nervous system remains to be elucidated. Here, we show that mRNA was highly expressed during neurodevelopment activated distributed throughout developing neurons, including neurites. The isolated neurite culture time-lapse imaging demonstrated neurites brain-derived...
Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck the difficulty in modeling depressive episodes animals. Here, we show that transgenic mouse with chronic forebrain expression dominant negative mutant Polg1, mitochondrial DNA (mtDNA) polymerase, exhibits lethargic behavioral changes, which are associated emotional, vegetative and psychomotor disturbances, response to antidepression drug treatment. The results suggested...
Abstract Large-scale genome-wide association studies (GWASs) on bipolar disorder (BD) have implicated the involvement of fatty acid desaturase ( FADS ) locus. These enzymes (FADS1 and FADS2) are involved in metabolism eicosapentaenoic (EPA) docosahexaenoic (DHA), which thought to potentially benefit patients with mood disorders. To model reductions activity FADS1/2 affected by susceptibility alleles, we generated mutant mice heterozygously lacking both Fads1 / 2 genes. We measured...
Impaired endoplasmic reticulum (ER) stress response has been suggested as a possible pathophysiological mechanism of bipolar disorder (BD). The expression ER stress-related genes, spliced form or unspliced XBP1, GRP78 (HSPA5), GRP94 (HSP90B1), CHOP (DDIT3), and calreticulin (CALR), were examined in lymphoblastoid cells derived from 59 patients with BD age- sex-matched control subjects. Basal mRNA levels induction by 4 h 12 treatment two stressors, thapsigargin tunicamycin, using real-time...
Diagnostic biomarkers of major depressive disorder, bipolar and schizophrenia are urgently needed, because none currently available.We performed a comprehensive metabolome analysis plasma samples from drug-free patients with disorder (n=9), (n=6), (n=17), matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect diagnosis was found for 2 metabolites: nervonic acid cortisone, being the most significantly altered. The...
Avian cryptochrome 4 (Cry4) protein is a putative magnetosensitive molecule facilitating precise long-distance navigation in migratory birds. Two splice variants of Cry4 were reported European robin (Erithacus rubecula), namely ErCry4a and ErCry4b. It known that exhibits electron transfer between the flavin adenine dinucleotide (FAD) cofactor tryptophan residues generates magnetically sensitive radical pairs for magnetoreception. However, little about ErCry4b isoform. We therefore...
In a transcription/translation-based autoregulatory feedback loop of vertebrate circadian clock systems, BMAL1-CLOCK heterodimer is positive regulator for the transcription negative element gene Per. The chicken pineal gland represents photosensitive tissue, but genes constituting oscillator have been less well characterized.We identified expression Per2, Bmal1, Bmal2 and Clock in gland. Messenger RNA levels these exhibited overt rhythms cells, both vivo culture. vitro functional analyses...
Abstract Recent studies have consistently demonstrated that the regulation of chromatin and gene transcription plays a pivotal role in pathogenesis neurodevelopmental disorders. Among many genes involved these pathways, KMT2C , encoding one six known histone H3 lysine 4 (H3K4) methyltransferases humans rodents, was identified as whose heterozygous loss-of-function variants are causally associated with autism spectrum disorder (ASD) Kleefstra syndrome phenotypic spectrum. However, little is...
There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma in drug-free patients with BD SZ.We comprehensively analyzed metabolites using capillary electrophoresis time-of-flight mass spectrometry SZ (n = 17), 6), major depressive 9) who had not received psychotropics at least 2 weeks, matched healthy controls...
Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' common complex disease, are challenging because impacts variants on disease development difficult to substantiate. This study aimed examine amino acid substitution in POLG1 found bipolar disorder, as an example and proof concept, three different modalities assessment: silico predictions, vitro biochemical assays, clinical evaluation. We then tested whether deleterious contributed genetics...
Abstract Cardiolipin (CL) is a hallmark phospholipid of mitochondria and plays significant role in maintaining the mitochondrial structure functions. Despite physiological importance CL, mutant organisms, yeast, Arabidopsis , C elegans Drosophila which lack CL synthase ( Crls1 ) gene consequently are deprived viable. Here we report conditional ‐deficient mice using targeted insertion loxP sequences flanking functional domain CRLS1 enzyme. Homozygous null exhibited early embryonic lethality...
The hormone melatonin is synthesized from serotonin by two enzymatic reactions (AANAT and ASMT/HIOMT) in the pineal gland following a circadian rhythm with low levels during day high at night. robust nightly peak of secretion an output signal clock to whole organism. However, so far regulatory roles endogenous mammalian biological rhythms physiology processes are poorly understood. Here, we establish congenic mouse lines (>N10 generations) that proficient or deficient synthesis (AH+/+ AH-/-...
Increased levels of lactate, an end-product glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These in lactate can result decreased brain pH, which has implicated patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed five mouse models schizophrenia, bipolar disorder, and autism, suggesting shared endophenotype among these disorders rather than mere artifacts due...