title: Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression.
abstract: Stress has been shown to interact with genetic vulnerability in pathogenesis of psychiatric disorders. Here we investigated the outcome of interaction between genetic vulnerability and early-life stress, by employing a rodent model that combines an inherited trait of vulnerability in Flinders Sensitive Line (FSL) rats, with early-life stress (maternal separation). Basal differences in synaptic signaling between FSL rats and their controls were studied, as well as the consequences of early-life stress in adulthood, and their response to chronic antidepressant treatment (escitalopram). FSL rats showed basal differences in the activation of synapsin I and Erk1/2, as well as in alpha CaM kinase II/syntaxin-1 and alpha CaM kinase II/NMDA-receptor interactions in purified hippocampal synaptosomes. In addition, FSL rats displayed a blunted response of Erk-MAP kinases and other differences in the outcome of early-life stress in adulthood. Escitalopram treatment restored some but not all alterations observed in FSL rats after early-life stress. The marked alterations found in key regulators of presynaptic release/neurotransmission in the basal FSL rats, and as a result of early-life stress, suggest synaptic dysfunction. These results show that early gene-environment interaction may cause life-long synaptic changes affecting the course of depressive-like behavior and response to drugs.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Daniela
authors.initials: D
authors.lastname: Tardito
authors.forename: Susanne H M
authors.initials: SH
authors.lastname: Gruber
authors.forename: Aram
authors.initials: A
authors.lastname: El Khoury
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000473:pathology / Q000648:ultrastructure; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008426:Maternal Deprivation; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000150:complications* / Q000209:etiology / Q000523:psychology; D013550:Swimming / Q000523:psychology; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016194:Receptors, N-Methyl-D-Aspartate; D050827:Syntaxin 1; D015283:Citalopram; D048049:Extracellular Signal-Regulated MAP Kinases