Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression

• Published in: Journal of psychiatric research 2010-06, Vol.44 (8), p.511-520
• Main Authors: Musazzi, Laura, Mallei, Alessandra, Tardito, Daniela, Gruber, Susanne H.M, El Khoury, Aram, Racagni, Giorgio, Mathé, Aleksander A, Popoli, Maurizio
• Format: Article
• Language: English
• Subjects: Adulthood; Animal models; Animals; Animals, Newborn; Antidepressant; Antidepressant drugs; Antidepressants; Antidepressive Agents, Second-Generation - pharmacology; Antidepressive Agents, Second-Generation - therapeutic use; citalopram; Citalopram - pharmacology; Citalopram - therapeutic use; Depression; Depression - drug therapy; Depression - genetics; Depression - pathology; Disease Models, Animal; Drugs; Early-life stress; Erk-MAP kinases; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation - genetics; Hippocampus; Hippocampus - pathology; Hippocampus - ultrastructure; Immunoprecipitation - methods; Male; Maternal Deprivation; Medicin och hälsovetenskap; Mental disorders; Neurotransmission; Psychiatry; Random Allocation; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - physiology; Statistics, Nonparametric; Stress; Stress, Psychological - complications; Stress, Psychological - etiology; Stress, Psychological - psychology; Swimming - psychology; Synapsin I; Synaptic signaling; Synaptosomes; Synaptosomes - drug effects; Synaptosomes - physiology; syntaxin 1; Syntaxin 1 - metabolism; Vulnerability
• ISSN: 0022-3956; 1879-1379; 1879-1379
• DOI: 10.1016/j.jpsychires.2009.11.008

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 αCaM kinase II/syntaxin-1 and αCaM 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.