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  • Altered cell cycle dynamics in schizophrenia

    Author(s)
    Fan, Yongjun
    Abrahamsen, Greger
    McGrath, John J
    Mackay-Sim, Alan
    Griffith University Author(s)
    Mackay-Sim, Alan
    McGrath, John J.
    Abrahamsen, Greger
    Fan, Yongjun
    Year published
    2012
    Metadata
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    Abstract
    Background The olfactory mucosa, the organ of smell in the nose, is a neural tissue that regenerates new sensory neurons throughout adult life. Based on this tissue, we previously demonstrated increased mitosis in olfactory biopsy cultures from schizophrenia patients compared with healthy control subjects. In addition, neural stem/progenitor cell cultures (neurosphere-derived cells) from nasal biopsies from individuals with schizophrenia show significantly altered gene and protein expression in key cellcycle control pathways. Methods The aim of this study was to investigate cellcycledynamicsin olfactory neurosphere-derived ...
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    Background The olfactory mucosa, the organ of smell in the nose, is a neural tissue that regenerates new sensory neurons throughout adult life. Based on this tissue, we previously demonstrated increased mitosis in olfactory biopsy cultures from schizophrenia patients compared with healthy control subjects. In addition, neural stem/progenitor cell cultures (neurosphere-derived cells) from nasal biopsies from individuals with schizophrenia show significantly altered gene and protein expression in key cellcycle control pathways. Methods The aim of this study was to investigate cellcycledynamicsin olfactory neurosphere-derived cells from nine male schizophrenia patients and nine male healthy control subjects. Cellcycles were arrested by serum deprivation after which cell population doubling time, proliferation fraction, and cellcycle period were calculated from cell counts over 96 hours. Cellcycle phase was investigated using flow cytometry. Cell lysates were analyzed for expression of cyclin proteins. Results Cell population proliferation rate was increased inschizophrenia through a larger pool of proliferating progenitors and a reduced cellcycle period. All phases of the cellcycle were phase-shifted by 2 hours in the schizophrenia-derived cells, which expressed higher levels of the cyclins D1, E, and A2. Conclusions Our observations indicate that schizophrenia is associated with subtle alterations incellcycledynamics, shortening of the cellcycle period, and increased expression of G1/S phase cyclins. We speculate that this underlying diathesis could alter the temporal and spatial cascade of brain development and contribute to an altered neurodevelopmental trajectory inschizophrenia.
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    Journal Title
    Biological Psychiatry
    Volume
    71
    Issue
    2
    DOI
    https://doi.org/10.1016/j.biopsych.2011.10.004
    Subject
    Neurosciences not elsewhere classified
    Mental Health
    Biological Sciences
    Medical and Health Sciences
    Psychology and Cognitive Sciences
    Publication URI
    http://hdl.handle.net/10072/48598
    Collection
    • Journal articles

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