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.
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 schizophreniapatients 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 schizophreniapatients have altered cell adhesion, cell motility, and focal adhesion dynamics. METHODS: Olfactory neurosphere-derived cells from nine male schizophreniapatients 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.
Authors: Yasue Horiuchi; Shin-Ichi Kano; Koko Ishizuka; Nicola G Cascella; Seiji Ishii; C Conover Talbot; Andrew E Jaffe; Hideyuki Okano; Jonathan Pevsner; Carlo Colantuoni; Akira Sawa Journal: Neurosci Res Date: 2013-10-11 Impact factor: 3.304
Authors: Nikkie F M Olde Loohuis; Nael Nadif Kasri; Jeffrey C Glennon; Hans van Bokhoven; Sébastien S Hébert; Barry B Kaplan; Gerard J M Martens; Armaz Aschrafi Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2016-02-27 Impact factor: 5.067
Authors: Robin F Chan; Andrey A Shabalin; Carolina Montano; Eilis Hannon; Christina M Hultman; Margaret D Fallin; Andrew P Feinberg; Jonathan Mill; Edwin J C G van den Oord; Karolina A Aberg Journal: Schizophr Bull Date: 2020-02-26 Impact factor: 9.306
Authors: Soumya Narayan; Charlee McLean; Akira Sawa; Sandra Y Lin; Narayan Rai; MariaMananita S Hipolito; Nicola Cascella; John J I Nurnberger; Koko Ishizuka; Evaristus A Nwulia Journal: J Vis Exp Date: 2014-12-04 Impact factor: 1.355