Background
Recent studies on GTPases have suggested that reduced Duo and cell division cycle
42 (Cdc42) transcript expression is involved in dendritic spine loss in schizophrenia.
In murine models, Duo and Cdc42 phosphorylate p21-activated kinase 1 (PAK1), which
modifies the activity of regulatory myosin light chain (MLC) and cofilin by altering
their phosphorylation. Therefore, we hypothesized that in schizophrenia abnormal Duo
and Cdc42 expression result in changes in MLC and/or cofilin phosphorylation, which
might alter actin cytoskeleton dynamics underlying dendritic spine maintenance.
Methods
We performed Western blot protein expression analysis in postmortem brains from patients
diagnosed with schizophrenia and a comparison group. We focused our studies in the
anterior cingulate cortex (ACC; n = 33 comparison group; n = 36 schizophrenia) and dorsolateral prefrontal cortex (DLPFC; n = 29 comparison group; n = 35 schizophrenia).
Results
In both ACC and DLPFC, we found a reduction of Duo expression and PAK1 phosphorylation
in schizophrenia. Cdc42 protein expression was decreased in ACC but not in DLPFC.
In ACC, we observed decreased PAK1 phosphorylation and increased MLC phosphorylation
(pMLC), whereas in DLPFC pMLC remained unchanged.
Conclusions
These data suggest a novel mechanism that might underlie dendritic spine loss in schizophrenia.
The increase in pMLC seen in ACC might be associated with dendritic spine shrinkage.
The lack of an effect on pMLC in DLPFC suggests that in schizophrenia PAK1 downstream
pathways are differentially affected in these cortical areas.
Key Words
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Article info
Publication history
Published online: March 29, 2012
Accepted:
February 9,
2012
Received in revised form:
February 7,
2012
Received:
November 8,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
