Focal adhesion dynamics are altered in schizophrenia

Fan, Yongjun, Abrahamsen, Greger, Mills, Richard, Calderon, Claudia C., Tee, Jing Yang, Leyton, Lisette, Murrell, Wayne, Cooper-White, Justin, McGrath, John J. and Mackay-Sim, Alan (2013) Focal adhesion dynamics are altered in schizophrenia. Biological Psychiatry, 74 6: 418-426. doi:10.1016/j.biopsych.2013.01.020


Author 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
Title Focal adhesion dynamics are altered in schizophrenia
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
1873-2402
Publication date 2013-09-15
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2013.01.020
Open Access Status DOI
Volume 74
Issue 6
Start page 418
End page 426
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Language eng
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.
Formatted 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.
Keyword Cell migration
Disease model
Neurodevelopment
Patient-derived
Schizophrenia
Stem cell
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID DP110104446
1110149
R03TW007810
P09-015-F
ACT1111
Institutional Status UQ

 
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Created: Tue, 04 Jun 2013, 19:50:22 EST by Sheila Cleary on behalf of Psychiatry - Royal Brisbane and Women's Hospital