Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signalling

Purpose

The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study was to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease.
Experimental design

Network analysis was performed integrating pre-existing proteomic data from rodent models of depression. The IntAct mouse and the HRPD were used as reference protein-protein interaction databases. The functionality analyses of the networks were then performed by testing over-represented GO biological process terms and pathways.
Results

Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants were modulated, including glutamatergic signalling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms were implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping.
Conclusions and clinical relevance

This systems biology study supports the notion that animal models could contribute to the research into the biology and therapeutics of depression.