Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia

Matsumoto, Junya; Nakanishi, Hiroki; Kunii, Yasuto; Yuki, Dai; Wada, Akira; Hino, Mizuki; Niwa, Shin Ichi; Kondo, Takeshi; Waki, Michihiko; Hayasaka, Takahiro; Nio, Masaki; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Sato, Shinji; Sasaki, Takehiko; Setou, Mitsutoshi

doi:10.1038/srep45050

Cited by 23 publications

(51 citation statements)

References 54 publications

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“…7a), while the other metabolites remained unchanged (Figs. 7b-g) [[15], [16], [17]] (Supplementary Table 11). SAM contents showed a decreased trend ( p < 0.1), whereas SAH levels were unaltered in the schizophrenia group, resulting in reduced SAM/SAH ratio in the schizophrenic brain ( p < 0.01) (Figs.…”

Section: Resultsmentioning

confidence: 99%

“…Postmortem brain tissues (BA17; Brodmann Area 17) from schizophrenia and age-matched control samples were obtained from the Postmortem Brain Bank of Fukushima for Psychiatric Research and Brain Research Institute, Niigata University, Japan (in total n = 24 for schizophrenia and n = 31 for control) [[15], [16], [17]]. Each individual with schizophrenia fulfilled the diagnostic criteria established by the American Psychiatric Association (Diagnostic and Statistical Manual of Mental Disorders: DSM-IV) and had no history of any other neurological disorder or substance abuse.…”

Section: Methodsmentioning

confidence: 99%

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Investigation of betaine as a novel psychotherapeutic for schizophrenia

et al. 2019

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Background Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. Methods 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. Findings The Chdh -deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. 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 (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. 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. Interpretation The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. Fund This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018–2809 (YK) and RIKEN Epigenetics ...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Investigation of betaine as a novel psychotherapeutic for schizophrenia

et al. 2019

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“…Postmortem brain tissues (BA17; Brodmann Area 17) from schizophrenia and age-matched control samples were obtained from the Postmortem Brain Bank of Fukushima for Psychiatric Research and Brain Research Institute, Niigata University, Japan (in total n = 24 for schizophrenia and n = 31 for control) (16)(17)(18). Each individual with schizophrenia fulfilled the diagnostic criteria established by the American Psychiatric Association (Diagnostic and Statistical Manual of Mental Disorders: DSM-IV) and had no history of any other neurological disorder or substance abuse.…”

Section: Postmortem Brain Samplesmentioning

confidence: 99%

Investigation of betaine as a novel psychotherapeutic for schizophrenia

Ohnishi

Balan

Toyoshima

et al. 2019

Preprint

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Number of words in the abstract: 217 Number of words in the article body: 4714 Number of figures: 8 Number of tables: 0 Number of supplementary information: 1 -Number of supplementary tables: 13 -Number of supplementary figures: 10 2 ABSTRACTBetaine 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.

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“…MSI has been widely used in mapping lipids in mouse brain tissues, including fatty acids (Hirahara et al, ; Ibrahim et al, ; Lerner et al, ; Wu, Comi, Li, Rubakhin, & Sweedler, ; Zhou et al, ), ceramides (Barbacci et al, ; Muller et al, ; Nielsen et al, ; Woods et al, ), cardiolipins (Amoscato et al, ; Sparvero et al, ), phospholipids (Angel, Spraggins, Baldwin, & Caprioli, ; Guo et al, ; Hama et al, ; Hankin et al, ; Jadoul et al, ; Janfelt et al, ; Koizumi et al, ; Landgraf et al, ; Matsumoto et al, , ; Miyawaki et al, ; Shanta et al, ; Smith et al, ; Sparvero et al, ; Sugiura et al, ; Wang et al, ; Wang, Wang, & Han, ; Whitehead et al, ; Zaima et al, ), and sphingolipids (Caughlin et al, , ; Caughlin, Park, Yeung, Cechetto, & Whitehead, ; Chan et al, ; Dufresne et al, ; Ermini et al, ; Goto‐Inoue et al, ; Jackson et al, , ; Jones et al, ; Meriaux, Franck, Wisztorski, Salzet, & Fournier, ; Sugiura, Shimma, Konishi, Yamada, & Setou, ; Weishaupt, Caughlin, Yeung, & Whitehead, ; Whitehead et al, ). Gangliosides, amphipathic molecules composed of a ceramide lipid anchor linked to an oligosaccharide, are sialic acid‐containing glycosphingolipids and play numerous important roles in neuronal functions.…”

Section: Msi‐based Lipidomicsmentioning

confidence: 99%

Recent advances in mass spectrometry imaging for multiomics application in neurology

Gao

2018

J of Comparative Neurology

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Mass spectrometry imaging (MSI) has emerged as a powerful tool for multiomics study in neurology. MSI combines the multichannel (m/z) measurement capability of mass spectrometers with a surface sampling process that allows for rapid probing and mapping of the characterized intact proteins, proteolytic digested peptides, released glycans, phospholipids, glycolipids, and small metabolites in brain tissues. The present review is focused on the application of MSI to the study of proteomics, glycomics, peptidomics, metabolomics, and lipidomics in mouse brain tissues. K E Y W O R D Smass spectrometry imaging, mouse brain,

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Decreased 16:0/20:4-phosphatidylinositol level in the post-mortem prefrontal cortex of elderly patients with schizophrenia

Cited by 23 publications

References 54 publications

Investigation of betaine as a novel psychotherapeutic for schizophrenia

Investigation of betaine as a novel psychotherapeutic for schizophrenia

Investigation of betaine as a novel psychotherapeutic for schizophrenia

Recent advances in mass spectrometry imaging for multiomics application in neurology

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