Differential expression of synaptic proteins after chronic restraint stress in rat prefrontal cortex and hippocampus

Prolonged stress has been associated with altered synaptic plasticity but little is known about the molecular components and mechanisms involved in the stress response. In this study, we examined the effect of chronic restraint stress (CRS) on the expression of genes associated with synaptic vesicle exocytosis in rat prefrontal cortex and hippocampus. Rats were stressed daily using a 21day restraint stress paradigm, with durations of half an hour or 6h. RNA and protein were extracted from the same tissue sample and used for real-time quantitative polymerase chain reaction (real-time qPCR) and immunoblotting, respectively. Focusing on the SNARE complex, we investigated the expression of the SNARE core components syntaxin 1A, SNAP-25, and VAMP2 at both transcriptional and protein levels. In addition, the expression of 10 SNARE regulatory proteins was investigated at the transcriptional level. Overall, the prefrontal cortex was more sensitive to CRS compared to the hippocampus. In prefrontal cortex, CRS induced increased mRNA levels of VAMP2, VAMP1, syntaxin 1A, snapin, synaptotagmins I and III, and synapsins I and II, whereas SNAP-25 was down-regulated after CRS. Immunoblotting demonstrated equivalent changes in protein levels of VAMP2, syntaxin 1A, and SNAP-25. In hippocampus, we found increased mRNA levels of VAMP2 and SNAP-29 and a decrease in VAMP1 levels. Immunoblotting revealed decreased VAMP2 protein levels despite increased mRNA levels. Changes in the expression of synaptic proteins may accompany or contribute to the morphological, functional, and behavioral changes observed in experimental models of stress and may have relevance to the pathophysiology of stress-related disorders.