Focal adhesion dynamics are altered in schizophrenia

No Thumbnail Available
File version
Author(s)
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
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
2013
Size
File type(s)
Location
License
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.

Journal Title

Biological Psychiatry

Conference Title
Book Title
Edition
Volume

74

Issue

6

Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject

Biological sciences

Biomedical and clinical sciences

Neurosciences not elsewhere classified

Psychology

Persistent link to this record
Citation
Collections