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

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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.

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Acknowledgements

The authors would like to acknowledge the contributions of the Biological Mass Spectrometry and Proteomics Facility in the Department of Biological Sciences, University of Warwick. This project was funded by the Medical Research Council of South Africa and the National Research Foundation. Escitalopram was kindly donated by H. Lundbeck A/S, Denmark.

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Authors and Affiliations

  1. Division of Medical Physiology, University of Stellenbosch, PO Box 19063, Tygerberg, 7505, South Africa

    Lelanie Marais & Suzél M. Hattingh

  2. Department of Psychiatry, University of Cape Town, Cape Town, South Africa

    Dan J. Stein

  3. Discipline of Human Physiology, University of Kwazulu-Natal, Durban, South Africa

    Willie M. U. Daniels

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  1. Lelanie Marais
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  2. Suzél M. Hattingh
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Correspondence to Lelanie Marais.

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Marais, L., Hattingh, S.M., Stein, D.J. et al. A proteomic analysis of the ventral hippocampus of rats subjected to maternal separation and escitalopram treatment. Metab Brain Dis 24, 569–586 (2009). https://doi.org/10.1007/s11011-009-9156-3

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