Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.
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 is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease.



Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways.



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 are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping.



This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression.
Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Lucia
L
Carboni
Life Sciences Research Unit, University of Luxembourg, Luxembourg.
Thanh-Phuong
TP
Nguyen
Centre for Computational and Systems Biology (COSBI), The Microsoft Research-University of Trento, Trento, Italy.|Aptuit (Verona), Verona, Italy.
Laura
L
Caberlotto
D000818:Animals; D003865:Major Depressive Disorder / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D040901:Proteomics; D051381:Rats; D015398:Signal Transduction; D049490:Systems Biology
D018698:Glutamic Acid
Chronic mild stress; Inflammation; Major depression; Network analysis; Neurotrophic factors