| 1 | Biol. Psychiatry 2010 Jul 68: 25-32 |
|---|---|
| PMID | 20385374 |
| Title | Altered cortical CDC42 signaling pathways in schizophrenia: implications for dendritic spine deficits. |
| Abstract | Spine density on the basilar dendrites of pyramidal neurons is lower in layer 3, but not in layers 5 and 6, in the dorsolateral prefrontal cortex (DLPFC) of subjects withschizophrenia。The expression of CDC42 (cell division cycle 42), a RhoGTPase that regulates the outgrowth of the actin cytoskeleton and promotes spine formation, is also lower inschizophrenia; however, CDC42 mRNA is lower across layers 3-6, suggesting that other lamina-specific molecular alterations are critical for the spine deficits in the illness. The CDC42 effector proteins 3 and 4 (CDC42EP3, CDC42EP4) are preferentially expressed in DLPFC layers 2 and 3, andCDC42EP3appears to assemble septin filaments in spine necks. Therefore, alterations inCDC42EP3could contribute to the lamina-specific spine deficits inschizophrenia。 We measured transcript levels of CDC42,CDC42EP3, CDC42EP4; their interacting proteins (septins [SEPT2, 3, 5, 6, 7, 8, and 11], anillin), and other spine-specific proteins (spinophilin, PSD-95, and synaptopodin) in the DLPFC from 31 subjects withschizophreniaand matched normal comparison subjects. The expression ofCDC42EP3mRNA was significantly increased by 19.7%, and SEPT7 mRNA was significantly decreased by 6.9% in subjects withschizophrenia。皮质水平的CDC42EP3and SEPT7 mRNAs were not altered in monkeys chronically exposed to antipsychotic medications. Activated CDC42 is thought to disrupt septin filaments transiently in spine necks, allowing the molecular translocations required for synaptic potentiation. Thus, altered CDC42 signaling viaCDC42EP3may perturb synaptic plasticity and contribute to the spine deficits observed in layer 3 pyramidal neurons inschizophrenia。 |
| SCZ Keywords | schizophrenia |