Abstract
Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release involving SNCA, SYN-1, and AP-3. Our results indicate that increased oxidative phosphorylation (COX5A, NDUFB7, NDUFS8, COX5B, and UQCRB) within the hippocampal CA regions is part of a stress-protection mechanism.
Highlights
Stress exposure can lead to serious illnesses such as depression and post-traumatic stress disorder and have fatal consequences [1,2,3]
The hippocampal proteome was analyzed by mass spectrometrybased proteomics and numerous proteins, differentially expressed in the different stress-response phenotypes, were identified
This finding was reproduced in the present study, which showed a general effect of 4 weeks of mild stress exposure on sucrose intake with a mean decrease of 23% (Fig. 2A) and no concurrent reduction of water intake
Summary
Stress exposure can lead to serious illnesses such as depression and post-traumatic stress disorder and have fatal consequences [1,2,3]. It is widely accepted that resiliency is not merely a lack of stress susceptibility, but it is an active process involving physiological as well as psychological adaptations. The hippocampal formation is believed to be implicated in the etiology of depression, potentially through an important role in stress responses (10 –12). Based on the role of the hippocampal formation in stress and stress-related psychiatric disorders, one might expect to find markers of stress-susceptibility/resilience in this region of the brain. The development of the chronic mild stress (CMS) rat model of depression was based on the rationale that stress can induce depression [13, 14]. Using the CMS paradigm we have repeatedly found that the majority of rats exposed to chronic mild stress show a gradual reduction in consumption of sucrose solution, indicating an anhedonic-like state. The remaining rats do not reduce their sucrose intake and appear resilient to the stress-induced effects on sucrose intake [17, 19, 20]
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