Neurodegeneration, Neuroprotection, and Disease-Oriented NeuroscienceResearch PaperRegulation of cytoskeleton machinery, neurogenesis and energy metabolism pathways in a rat gene-environment model of depression revealed by proteomic analysis

The development of major depression requires both genetic and environmental factors. A brain proteomic investigation on the genetic model of Flinders sensitive and resistant line (FSL-FRL) rats was performed. Maternal separation (MS) was also applied to identify protein networks affected by stress exposure, since early-life trauma is considered an important antecedent of depression. Hippocampus (HIP) and prefrontal/frontal cortex proteins were extracted and separated by 2-Dimensional (2-D) gel electrophoresis. After image analysis, significantly modulated proteins in the different conditions analysed were identified by mass spectrometry. The expression of proteins involved in energy metabolism, cellular localization and transport, cytoskeleton organization and apoptosis differed in the two lines. Maternal separation differently affected the genetic backgrounds, by modulating cytoskeleton and neuron morphogenesis proteins in FSL; energy metabolism, cellular localization, neuron differentiation and intracellular transport in FRL. The present work shows that different mechanisms could be involved in the pathophysiology of depression and the vulnerability to stress, suggesting possible new cellular pathways and key markers for the study of affective disorders.

Research highlights▶A proteomic analysis was performed on FSL and FRL rats after MS. ▶Lines differed in energy metabolism, cell localization, cytoskeleton and apoptosis. ▶MS affected cytoskeleton and morphogenesis proteins in FSL. ▶MS modulated energy metabolism, differentiation and intracellular transport in FRL.