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  • Focal adhesion dynamics are altered in schizophrenia

    Author(s)
    Fan, Yongjun
    Abrahamsen, Greger
    Mills, Richard
    Calderon, Claudia C
    Tee, Jing Yang
    Leyton, Lisette
    Murrell, Wayne
    Cooper-White, Justin
    McGrath, John J
    Mackay-Sim, Alan
    Griffith University Author(s)
    Mackay-Sim, Alan
    Year published
    2013
    Metadata
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    Abstract
    Background Evidence from genetic association studies implicate genes involved in neural migration associated with schizophrenia risk. Neural stem/progenitor cell cultures (neurosphere-derived cells) from olfactory mucosa of schizophrenia patients have significantly dysregulated expression of genes in focal adhesion kinase (FAK) signaling, a key pathway regulating cell adhesion and migration. The aim of this study was to investigate whether olfactory neurosphere-derived cells from schizophrenia patients have altered cell adhesion, cell motility, and focal adhesion dynamics. Methods Olfactory neurosphere-derived cells from ...
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    Background Evidence from genetic association studies implicate genes involved in neural migration associated with schizophrenia risk. Neural stem/progenitor cell cultures (neurosphere-derived cells) from olfactory mucosa of schizophrenia patients have significantly dysregulated expression of genes in focal adhesion kinase (FAK) signaling, a key pathway regulating cell adhesion and migration. The aim of this study was to investigate whether olfactory neurosphere-derived cells from schizophrenia patients have altered cell adhesion, cell motility, and focal adhesion dynamics. Methods Olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects were used. Cells were assayed for cell adhesion and cell motility and analyzed for integrins and FAK proteins. Focal adhesions were counted and measured in fixed cells, and time-lapse imaging was used to assess cell motility and focal adhesion dynamics. Results Patient-derived cells were less adhesive and more motile than cells derived from healthy control subjects, and their motility was reduced to control cell levels by integrin-blocking antibodies and by inhibition of FAK. Vinculin-stained focal adhesion complexes were significantly smaller and fewer in patient cells. Time-lapse imaging of cells expressing FAK tagged with green fluorescent protein revealed that the disassembly of focal adhesions was significantly faster in patient cells. Conclusions The evidence for altered motility and focal adhesion dynamics in patient-derived cells is consistent with dysregulated gene expression in the FAK signaling pathway in these cells. Alterations in cell adhesion dynamics and cell motility could bias the trajectory of brain development in schizophrenia.
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    Journal Title
    Biological Psychiatry
    Volume
    74
    Issue
    6
    DOI
    https://doi.org/10.1016/j.biopsych.2013.01.020
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Neurosciences not elsewhere classified
    Psychology
    Publication URI
    http://hdl.handle.net/10072/56932
    Collection
    • Journal articles

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