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タイトル: Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders
著者: Hagihara, Hideo
Catts, S., Vibeke
Katayama, Yuta
Shoji, Hirotaka
Takagi, Tsuyoshi
Huang, L., Freesia
Nakao, Akito  kyouindb  KAKEN_id
Mori, Yasuo  kyouindb  KAKEN_id
Huang, Kuo-Ping
Ishii, Shunsuke
Graef, A., Isabella
Nakayama, I., Keiichi
Weickert, Shannon, Cynthia
Miyakawa, Tsuyoshi
著者名の別形: 森, 泰生
発行日: Feb-2018
出版者: Springer Nature
誌名: Neuropsychopharmacology
巻: 43
号: 3
開始ページ: 459
終了ページ: 468
抄録: Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder.
著作権等: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
URI: http://hdl.handle.net/2433/234997
DOI(出版社版): 10.1038/npp.2017.167
PubMed ID: 28776581
出現コレクション:学術雑誌掲載論文等

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