Focal adhesion dynamics are altered in schizophrenia

Yongjun Fan, Greger Abrahamsen, Richard Mills, Claudia C. Calderón, Jing Yang Tee, Lisette Leyton, Wayne Murrell, Justin Cooper-White, John J. McGrath, Alan Mackay-Sim

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49 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)418-426
Number of pages9
JournalBiological Psychiatry
Volume74
Issue number6
DOIs
Publication statusPublished - 15 Sep 2013
Externally publishedYes

Keywords

  • Cell migration
  • disease model
  • neurodevelopment
  • patient-derived
  • schizophrenia
  • stem cell

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