Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression.
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.
Centre for Psychiatric Research, Institute of Clinical Medicine, Aarhus University Hospital, University of Aarhus, Risskov, Denmark. kimhenni@rm.dk
Kim
K
Henningsen
Johan
J
Palmfeldt
Sofie
S
Christiansen
Isabel
I
Baiges
Steffen
S
Bak
Ole Nørregaard
ON
Jensen
Niels
N
Gregersen
Ove
O
Wiborg
D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D010085:Oxidative Phosphorylation; D010775:Photic Stimulation / Q000009:adverse effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D013395:Sucrose / Q000008:administration & dosage; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D004268:DNA-Binding Proteins; C497606:Snca protein, rat; D016704:Synapsins; D014157:Transcription Factors; D051844:alpha-Synuclein; C060759:enhancer-binding protein AP-3; D013395:Sucrose