A proteomic analysis of the ventral hippocampus of rats subjected to maternal separation and escitalopram treatment
Date
2009
Authors
Marais L.
Hattingh S.M.
Stein D.J.
Daniels W.M.U.
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Abstract
Early life stress is known to predispose humans to the development of depression. Developmental stress has been shown to cause various changes in neurotransmitter systems, neurotrophin expression and the hypothalamic pituitary adrenal-axis in the rat brain. The aim of this study was to identify which cytosolic proteins are altered by maternal separation, as a model for depression, as well as by chronic antidepressant treatment. Rats were maternally separated from postnatal day 2-14 for 3 h per day while control rats were normally reared. Both groups were divided and received either escitalopram or saline injections for 6 weeks starting from postnatal day 40. The ventral hippocampal tissue was fractionated and the cytosolic fraction used for 2-D-gel electrophoresis and liquid chromatography coupled to mass spectrometry analyses to identify peptides. Mascot database searches were done to identify proteins that were differentially expressed between the groups. Proteins that were significantly changed by maternal separation included amongst others: molecular chaperones and proteins related to energy metabolism; neuroplasticity; oxidative stress regulation; and protein metabolism. Treatment with escitalopram, a selective-serotonin reuptake inhibitor, induced changes in a different group of proteins, except for a few involved in energy metabolism and neuroprotective pathways. The results indicate which cytosolic proteins are changed by early life stress and may therefore be involved in the development of depression. © 2009 Springer Science+Business Media, LLC.
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Keywords
amino acid, cell protein, corticotropin, cytosolic protein, escitalopram, neurotrophin, serotonin uptake inhibitor, unclassified drug, amino acid sequence, animal experiment, animal model, animal tissue, article, controlled study, corticotropin release, depression, disease predisposition, drug effect, electrospray mass spectrometry, energy metabolism, experimental model, hippocampus, hypothalamus hypophysis adrenal system, life stress, liquid chromatography, long term care, maternal deprivation, mother child relation, neurotransmission, newborn, nonhuman, nucleotide sequence, oxidative stress, perinatal period, protein expression, proteomics, psychopharmacotherapy, rat, two dimensional gel electrophoresis, unindexed sequence, Animals, Causality, Citalopram, Depressive Disorder, Disease Models, Animal, Energy Metabolism, Female, Hippocampus, Male, Maternal Deprivation, Molecular Chaperones, Nerve Tissue Proteins, Neuronal Plasticity, Oxidative Stress, Proteomics, Rats, Rats, Sprague-Dawley, Serotonin Uptake Inhibitors, Stress, Psychological, Time, Treatment Outcome, Rattus
Citation
Metabolic Brain Disease
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