Biology subjects

Yabe, H.

Publications and source records attributed to Yabe, H..

3 recordsLinked to original sources

bioRxiv2022

Lipid-correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia

BackgroundSchizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. A previous study showed that specific lipid molecules belong to phosphatidylinositol (PI) and phosphatidylserine (PS) was reduced in the postmortem prefrontal cortex of patients with schizophrenia1. However, signaling pathways contributing to the lipid changes remain unknown. Here we performed two types of transcriptome analyses in patients with schizophrenia: an un-biased transcriptome analysis solely based on RNA-seq data and a correlation analysis between levels of gene expression and lipids. Methodology/Principal FindingsRNA-Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects which are the same samples in the previous lipidomics study1 (Table 1). Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes of gene expression levels in phosphoinositide 3-kinase (PI3K)-Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in several signaling/metabolic pathways including lipid-correlated genes, most of which are not found as DEGs in transcriptome analysis alone. O_TBL View this table: org.highwire.dtl.DTLVardef@80d74eorg.highwire.dtl.DTLVardef@b780b7org.highwire.dtl.DTLVardef@1637f28org.highwire.dtl.DTLVardef@1315439org.highwire.dtl.DTLVardef@190a230_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable 1.C_FLOATNO O_TABLECAPTIONCharacteristics of patients from whom postmortem brain samples were obtained. Abbreviations: PMI, postmortem interval, the time that has elapsed since a person has died; DOI, duration of illness, The samples used in correlation analysis are shown by black circles. C_TABLECAPTION C_TBL ConclusionsThis study provided results of the first integrated analysis of the schizophrenia-associated transcriptome and lipidome within the PFC and revealed that lipid-correlated alterations in the transcriptome are enriched in specific pathways including PI3K-Akt signaling.

pathology↗

bioRxiv2020

Angiopathy with impaired glucose logistics observed in schizophrenia-like model mice

Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high-simple-sugar diets contribute to pathogenesis of these diseases. Here we demonstrate that a high-sucrose diet during adolescence induces psychosis-related behavioral endophenotypes, including hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function in mice deficient for glyoxalase-1 (Glo1), an enzyme involved in detoxification of sucrose metabolites. Further, the high-sucrose diet induced microcapillary impairments and reduced brain glucose uptake in brains of Glo1 deficient mice. Aspirin protected against this angiopathy, enhancing brain glucose uptake, and preventing abnormal behavioral phenotypes. Similar vascular damage to our model mice was found in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.

neuroscience↗

bioRxiv2019

Investigation of betaine as a novel psychotherapeutic for schizophrenia

Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine treatments. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with \"betaine deficit-oxidative stress pathology\". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. In conclusion, the present study underscores the potential benefit of betaine in a subset of schizophrenia.

neuroscience↗