A proteomic analysis of the ventral hippocampus of rats subjected to maternal separation and escitalopram treatment

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.

Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation

“…As it is beyond the scope of this paper to discuss all the identified proteins in detail, we will mainly focus on the proteins whose expression was significantly altered by exercise in normally reared animals and those proteins that were significantly altered by MS but subsequently restored by exercise. The effects of MS alone on the expression of proteins in the ventral hippocampus have been reported in a previous independent study (Marais et al 2009a). …”

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum

“…Our results partly correlate to data suggesting that escitalopram treatment induced changes in various rat hippocampal proteins (not neuropeptides), except for those involved in energy expenditure and neuroprotection [32] but it had no effect on hippocampal volume [33]. Interestingly administration of escitalopram during adolescence could modify the alterations of increased choline-containing compounds and decreased glutamate, N-acetylaspartate and myoinositol relative to the stable neurometabolite creatine in rat hippocampus [33].…”

Chronic agomelatine treatment corrects behavioral, cellular, and biochemical abnormalities induced by prenatal stress in rats

“…Agomelatine treatment preferentially enhanced neurogenesis in the ventral hippocampus of PRS rats as it does in transgenic mice with defective glucocorticoid receptors (Païzanis et al 2010). Other antidepressant drugs also affect the neurogenesis in the ventral hippocampus in different animal models of depression (Bisgaard et al 2007;Jayatissa et al 2006;Marais et al 2009;Surget et al 2008). Remarkably, agomelatine and fluoxetine treatment did not affect the hippocampal neurogenesis in control rats under the given experimental conditions.…”