Decreased Brain pH and Pathophysiology in Schizophrenia

• Type of Material: Article
• Authors: Hae-Jeong Park, Kyung Hee University; Inyeong Choi, Emory University; Kang-Hyun Leem, Semyung University
• Language: English
• Date: 2021-08-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/ijms22168358
• Title of Journal or Parent Work: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: 22
• Issue: 16
• Grant/Funding Information: This study was supported by grants from Medical Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (NRF-2017R1A5A2014768).
• Keywords: Biochemistry & Molecular Biology; METHYL-D-ASPARTATE; Science & Technology; Life Sciences & Biomedicine; Physical Sciences; PREFRONTAL CORTEX; NMDA RECEPTOR BLOCKADE; Chemistry, Multidisciplinary; BLOOD LACTATE LEVELS; MENTAL-RETARDATION; Chemistry; MITOCHONDRIAL DYSFUNCTION; MEMBRANE PHOSPHOLIPID-METABOLISM; glutamate; schizophrenia; brain pH; NA+/H+ EXCHANGER; RENAL OK CELLS; NEUROTROPHIC FACTOR; mitochondria dysfunction; dopamine; lactate; pH-regulating proteins
• Research Categories: Health Sciences, Pharmacology

Abstract

Postmortem studies reveal that the brain pH in schizophrenia patients is lower than normal. The exact cause of this low pH is unclear, but increased lactate levels due to abnormal energy metabolism appear to be involved. Schizophrenia patients display distinct changes in mitochondria number, morphology, and function, and such changes promote anaerobic glycolysis, elevating lactate levels. pH can affect neuronal activity as H+ binds to numerous proteins in the nervous system and alters the structure and function of the bound proteins. There is growing evidence of pH change associated with cognition, emotion, and psychotic behaviors. Brain has delicate pH regulatory mechanisms to maintain normal pH in neurons/glia and extracellular fluid, and a change in these mechanisms can affect, or be affected by, neuronal activities associated with schizophrenia. In this review, we discuss the current understanding of the cause and effect of decreased brain pH in schizophrenia based on postmortem human brains, animal models, and cellular studies. The topic includes the factors causing decreased brain pH in schizophrenia, mitochondria dysfunction leading to altered energy metabolism, and pH effects on the pathophysiology of schizophrenia. We also review the acid/base transporters regulating pH in the nervous system and discuss the potential contribution of the major transporters, sodium hydrogen exchangers (NHEs), and sodium-coupled bicarbonate transporters (NCBTs), to schizophrenia.