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    Measurement of lactate levels in postmortem brain, iPSCs, and animal models of schizophrenia.

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    Author
    Sullivan, Courtney R
    Mielnik, Catharine A
    Funk, Adam
    Rowland, Laura M
    Date
    2019-03-25
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1038/s41598-019-41572-9
    Abstract
    Converging evidence suggests bioenergetic defects contribute to the pathophysiology of schizophrenia and may underlie cognitive dysfunction. The transport and metabolism of lactate energetically couples astrocytes and neurons and supports brain bioenergetics. We examined the concentration of lactate in postmortem brain (dorsolateral prefrontal cortex) in subjects with schizophrenia, in two animal models of schizophrenia, the GluN1 knockdown mouse model and mutant disrupted in schizophrenia 1 (DISC1) mouse model, as well as inducible pluripotent stem cells (iPSCs) from a schizophrenia subject with the DISC1 mutation. We found increased lactate in the dorsolateral prefrontal cortex (p = 0.043, n = 16/group) in schizophrenia, as well as in frontal cortical neurons differentiated from a subject with schizophrenia with the DISC1 mutation (p = 0.032). We also found a decrease in lactate in mice with induced expression of mutant human DISC1 specifically in astrocytes (p = 0.049). These results build upon the body of evidence supporting bioenergetic dysfunction in schizophrenia, and suggests changes in lactate are a key feature of this often devastating severe mental illness. © 2019, The Author(s).
    Keyword
    astrocyte-neuron lactate shuttle
    Energy Metabolism--physiology
    Lactic Acid
    Prefrontal Cortex
    Schizophrenia--physiopathology
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/8845
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-019-41572-9
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    UMB Open Access Articles 2019

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