Protein biomarkers of susceptibility and resilience to stress in a rat model of depression.
The molecular etiologies of psychological stress and major depressive disorder (MDD) are highly complex and many brain regions are involved. The prefrontal cortex (PFC) has gained attention in depression research due to its role in cognition including working memory and decision-making, which are impaired in MDD. The aim of the present study was to identify differentially regulated synaptosomal proteins from PFC in stress-exposed animals. The well-established chronic mild stress (CMS) rodent model was applied and three groups of rats were studied: unstressed controls, stress-susceptible and stress resilient. Large-scale proteomics based on relative iTRAQ quantification was applied on three synaptosomal Percoll gradient fractions and 27 proteins were found to undergo significant differential regulation. Gradient fraction two (F2) contained the highest amounts of synaptosomal proteins and is therefore recommended to be included in proteomic studies onwards, in addition to the traditionally used fractions F3 and F4. The regulated proteins corroborate previous studies on depression regulated proteins; including GFAP, HOMER1 and glutamatergic transmission (vesicular transporter 1, VGLUT1). However, additional functionalities were represented - especially in stress-resilient rats - such as oxidative stress protection (peroxiredoxins PRDX1 and PRDX2), Na/K-transporter ATP1A2 and respiratory chain subunits (UQCRC1 and UQCRFS1), which illustrate the biochemical complexity behind the stress phenotypes, but may also aid in the development of novel treatment strategies.
Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University Hospital, University of Aarhus, Aarhus N, Denmark.
Johan
J
Palmfeldt
Translational Neuropsychiatry Unit, Department of Clinical Medicine, University of Aarhus, Risskov, Denmark. Electronic address: kimhenni@gmail.com.
Kim
K
Henningsen
Translational Neuropsychiatry Unit, Department of Clinical Medicine, University of Aarhus, Risskov, Denmark.
Stine Aistrup
SA
Eriksen
Translational Neuropsychiatry Unit, Department of Clinical Medicine, University of Aarhus, Risskov, Denmark.
Heidi K
HK
Müller
Translational Neuropsychiatry Unit, Department of Clinical Medicine, University of Aarhus, Risskov, Denmark.
Ove
O
Wiborg
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D000072233:Homer Scaffolding Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D050598:Vesicular Glutamate Transport Protein 1 / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase
Biomarkers; Chronic mild stress model of depression; Glial fibrillary acidic protein; Prefrontal cortex; Synaptosome