51. Early-life stress and antidepressant treatment involve synaptic signaling and Erk kinases in a gene-environment model of depression
- Author
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Aram El Khoury, Maurizio Popoli, Giorgio Racagni, Alessandra Mallei, Laura Musazzi, Susanne H.M. Gruber, Aleksander A. Mathé, Daniela Tardito, Musazzi, L, Mallei, A, Tardito, D, Gruber, S, El Khoury, A, Racagni, G, Mathé, A, and Popoli, M
- Subjects
Male ,medicine.medical_specialty ,Synapsin I ,Early-life Stre ,Syntaxin 1 ,Antidepressant ,Neurotransmission ,Citalopram ,Hippocampus ,Receptors, N-Methyl-D-Aspartate ,Statistics, Nonparametric ,psychiatric disorder ,Rats, Sprague-Dawley ,Random Allocation ,Internal medicine ,Ca2+/calmodulin-dependent protein kinase ,medicine ,Animals ,Immunoprecipitation ,Extracellular Signal-Regulated MAP Kinases ,Biological Psychiatry ,Swimming ,Maternal deprivation ,biology ,Depression ,animal model ,Maternal Deprivation ,Rats, Inbred Strains ,Rats ,Psychiatry and Mental health ,Disease Models, Animal ,Endocrinology ,Gene-Environment interaction ,Animals, Newborn ,Gene Expression Regulation ,Mitogen-activated protein kinase ,biology.protein ,NMDA receptor ,Antidepressive Agents, Second-Generation ,Synaptic signaling ,Psychology ,Neuroscience ,Stress, Psychological ,Signal Transduction ,Synaptosomes - 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.
- Published
- 2009