| 1 | Biol. Psychiatry 2015 Dec 78: 775-85 |
|---|---|
| PMID | 25981171 |
| Title | Altered expression of CDC42 signaling pathway components in cortical layer 3 pyramidal cells in schizophrenia. |
| Abstract | Cognitive dysfunction inschizophreniais associated with a lower density of dendritic spines on deep layer 3 pyramidal cells in the dorsolateral prefrontal cortex (DLPFC). These alterations appear to reflect dysregulation of the actin cytoskeleton required for spine formation and maintenance. Consistent with this idea, altered expression of genes in the cell division cycle 42 (CDC42)-CDC42 effector protein (CDC42EP) signaling pathway, a key organizer of the actin cytoskeleton, was previously reported in DLPFC gray matter from subjects withschizophrenia. We examined the integrity of the CDC42-p21-activated serine/threonine protein kinases (PAK)-LIM domain-containing serine/threonine protein kinases (LIMK) signaling pathway inschizophreniain a layer-specific and cell type-specific fashion in DLPFC deep layer 3. Using laser microdissection, samples of DLPFC deep layer 3 were collected from 56 matched pairs of subjects withschizophreniaand comparison subjects, and levels of CDC42-PAK-LIMK pathway messenger RNAs were measured by quantitative polymerase chain reaction. These same transcripts also were quantified by microarray in samples of individually microdissected deep layer 3 pyramidal cells from a subset of the same subjects and from monkeys exposed to antipsychotics. Relative to comparison subjects, CDC42EP4, LIMK1,LIMK2, ARHGDIA, and PAK3 messenger RNA levels were significantly upregulated in subjects withschizophreniain laminar and cellular samples. In contrast, CDC42 and PAK1 messenger RNA levels were significantly downregulated specifically in deep layer 3 pyramidal cells. These differences were not attributable to psychotropic medications or other comorbid factors. 从现在和之前的研究转换结果ge on synergistic alterations in CDC42 signaling pathway that could destabilize actin dynamics and produce spine deficits preferentially in deep layer 3 pyramidal cells inschizophrenia. |
| SCZ Keywords | schizophrenia |