title: Synaptoproteomic analysis of a rat gene-environment model of depression reveals involvement of energy metabolism and cellular remodeling pathways.
abstract: BACKGROUND
  Major depression is a severe mental illness that causes heavy social and economic burdens worldwide. A number of studies have shown that interaction between individual genetic vulnerability and environmental risk factors, such as stress, is crucial in psychiatric pathophysiology. In particular, the experience of stressful events in childhood, such as neglect, abuse, or parental loss, was found to increase the risk for development of depression in adult life. Here, to reproduce the gene x environment interaction, we employed an animal model that combines genetic vulnerability with early-life stress.
  
  
  METHODS
  The Flinders Sensitive Line rats (FSL), a validated genetic animal model of depression, and the Flinders Resistant Line (FRL) rats, their controls, were subjected to a standard protocol of maternal separation (MS) from postnatal days 2 to 14. A basal comparison between the two lines for the outcome of the environmental manipulation was performed at postnatal day 73, when the rats were into adulthood. We carried out a global proteomic analysis of purified synaptic terminals (synaptosomes), in order to study a subcellular compartment enriched in proteins involved in synaptic function. Two-dimensional gel electrophoresis (2-DE), mass spectrometry, and bioinformatic analysis were used to analyze proteins and related functional networks that were modulated by genetic susceptibility (FSL vs. FRL) or by exposure to early-life stress (FRL + MS vs. FRL and FSL + MS vs.
  We found that, at a synaptic level, mainly proteins and molecular pathways related to energy metabolism and cellular remodeling were dysregulated.
  
  
  CONCLUSIONS
  The present results, in line with previous works, suggest that dysfunction of energy metabolism and cytoskeleton dynamics at a synaptic level could be features of stress-related pathologies, in particular major depression.
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé). alessandra.mallei@unimi.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé).
authors.forename: Marion
authors.initials: M
authors.lastname: Failler
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé).
authors.forename: Stefano
authors.initials: S
authors.lastname: Corna
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé).
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé).
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.affiliation: Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento di Scienze Farmacologiche e Biomolecolari and Center of Excellence on Neurodegenerative Diseases, University of Milano, Milano, Italy (Drs Mallei, Failler, Corna, Racagni, and Popoli); Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (Dr Mathé).
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D019295:Computational Biology; D003863:Depression / Q000209:etiology* / Q000235:genetics*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000235:genetics*; D059647:Gene-Environment Interaction; D013058:Mass Spectrometry; D008426:Maternal Deprivation; D040901:Proteomics / Q000379:methods; D051381:Rats; D016708:Synaptophysin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D016708:Synaptophysin; C504262:Synpr protein, rat
keywords: early-life stress; frontal cortex; hippocampus; prefrontal cortex; proteomics; synaptosome