Evidence mapPaperPMID 34198071Full record

ArticleRedox biology2021

Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex.

Kazuya Toriumi, Stefano Berto, Shin Koike, Noriyoshi Usui, Takashi Dan, Kazuhiro Suzuki, Mitsuhiro Miyashita, Yasue Horiuchi, Akane Yoshikawa, Mai Asakura and 10 more

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 26 citations in OpenAlex.

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  15. Genetic polymorphism and neuroanatomical changes in schizophrenia.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 2 countries.

Kazuya ToriumiSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Stefano BertoDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29403, USA.
Shin KoikeDepartment of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.
Noriyoshi UsuiDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Center for Medical Research and Education, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan; Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan; Global Center for Medical Engineering and Informatics, Osaka University, Osaka, 565-0871, Japan.
Takashi DanDivision of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
Kazuhiro SuzukiSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan; Department of Psychiatry, Graduate School of Medicine, Shinshu University, Nagano, 390-8621, Japan.
Mitsuhiro MiyashitaSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.
Yasue HoriuchiSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.
Akane YoshikawaSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan; Department of Psychiatry and Behavioral Science, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
Mai AsakuraSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.
Kenichiro NagahamaDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Hsiao-Chun LinDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Yuki SugayaDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Takaki WatanabeDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Masanobu KanoDepartment of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Yuki OgasawaraDepartment of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.
Toshio MiyataDivision of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
Masanari ItokawaSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan.
Genevieve KonopkaDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.
Makoto AraiSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan. Electronic address: arai-mk@igakuken.or.jp.
Tokyo Metropolitan Matsuzawa Hospital · JPThe University of Tokyo · JPMeiji Pharmaceutical University · JPThe University of Texas Southwestern Medical Center · USTohoku University · JPMedical University of South Carolina · USShinshu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Methylglyoxal (MG) is a reactive and cytotoxic α-dicarbonyl byproduct of glycolysis. Our bodies have several bio-defense systems to detoxify MG, including an enzymatic system by glyoxalase (GLO) 1 and GLO2. We identified a subtype of schizophrenia patients with novel mutations in the GLO1 gene that results in reductions of enzymatic activity. Moreover, we found that vitamin B6 (VB6) levels in peripheral blood of the schizophrenia patients with GLO1 dysfunction are significantly lower than that of healthy controls. However, the effects of GLO1 dysfunction and VB6 deficiency on the pathophysiology of schizophrenia remains poorly understood. Here, we generated a novel mouse model for this subgroup of schizophrenia patients by feeding Glo1 knockout mice VB6-deficent diets (KO/VB6(-)) and evaluated the combined effects of GLO1 dysfunction and VB6 deficiency on brain function. KO/VB6(-) mice accumulated homocysteine in plasma and MG in the prefrontal cortex (PFC), hippocampus, and striatum, and displayed behavioral deficits, such as impairments of social interaction and cognitive memory and a sensorimotor deficit in the prepulse inhibition test. Furthermore, we found aberrant gene expression related to mitochondria function in the PFC of the KO/VB6(-) mice by RNA-sequencing and weighted gene co-expression network analysis (WGCNA). Finally, we demonstrated abnormal mitochondrial respiratory function and subsequently enhanced oxidative stress in the PFC of KO/VB6(-) mice in the PFC. These findings suggest that the combination of GLO1 dysfunction and VB6 deficiency may cause the observed behavioral deficits via mitochondrial dysfunction and oxidative stress in the PFC.

Indexed as

Lactoylglutathione LyaseSchizophreniaVitamin B 6 DeficiencyAnimalsHumansMiceMitochondriaPrefrontal CortexGlo1 protein, mouseLactoylglutathione LyaseGlyoxalase 1MethylglyoxalMitochondriaOxidative stressSchizophreniaVitamin B6

Identifiers

PMID34198071
PMCPMC8253914
OpenAlexW3176811330

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.