Altered cell cycle dynamics in schizophrenia

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 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.