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Chronic Exposure to Light Reverses the Effect of Maternal Separation on Proteins in the Prefrontal Cortex

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Abstract

Animals subjected to maternal separation display behavioural and endocrine disturbances, as well as structural and functional changes in the prefrontal cortex and limbic areas. The aim of the present study was to determine the effect of maternal separation and treatment with either chronic constant light exposure or anti-depressant (escitalopram) on proteins in the prefrontal cortex. Four experimental groups of male Sprague–Dawley rats were subjected to (1) normal rearing, (2) maternal separation (3 h per day from postnatal day 2 (P2) to P14), (3) maternal separation followed by chronic light exposure (P42-P63) or (4) maternal separation followed by treatment with the anti-depressant drug, escitalopram (P68-P100). Groups 1–3 were treated with saline as vehicle control for the escitalopram-treated group. At P101, all rats were decapitated, and the prefrontal cortex was collected and stored at −80 °C. Tissue from three rats per group was pooled and proteins determined by isobaric tagging for relative and absolute quantification using matrix-assisted laser desorption/ionisation tandem mass spectrometry. Maternal separation led to disruptions in the prefrontal cortex that included hypometabolism by decreasing energy-related proteins (creatine kinase B, aconitate hydratase), decreased cell signalling (synapsin I, calmodulin, 14-3-3 protein epsilon) and impaired plasticity (spectrin, microtubule-associated protein). Maternal separation also increased dihydropyrimidinase-related protein/collapsin response mediator protein (CRMP) and myelin proteolipid protein. Exposure of maternally separated animals to constant light during adolescence reversed the hypometabolic state by increasing energy-related proteins in the prefrontal cortex and increasing cell signalling and cytoskeletal proteins and decreasing the expression of CRMP. Escitalopram had similar effects to light by increasing ATP synthase in maternally separated rats and dissimilar effects by increasing 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin proteolipid protein. Constant light exposure during adolescence reversed a range of protein changes in the prefrontal cortex of rats exposed to early maternal separation. The most prominent reversal by light treatment of maternal separation-induced protein increases in the prefrontal cortex was the expression of CRMP which impairs plasticity and neuronal signalling. The effects of light treatment overlapped partially with the effects of escitalopram.

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Acknowledgements

The authors would like to acknowledge the contributions of the CPGR, the Institute for the Study of Affective Neuroscience (ISAN, grant no 9276) for financial support, the National Research Foundation (NRF), Harry Crossley Foundation for financial support of the postdoctoral fellow and Cipla Medpro (Pty) Ltd for their kind donation of escitalopram oxalate.

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Authors and Affiliations

  1. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, Anzio Road, Cape Town, 7925, South Africa

    J. J. Dimatelis & V. A. Russell

  2. Department of Psychiatry and Mental Health, Faculty of Health Sciences, University of Cape Town, Observatory, Cape Town, 7925, South Africa

    D. J. Stein

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  1. J. J. Dimatelis
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Correspondence to J. J. Dimatelis.

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Dimatelis, J.J., Stein, D.J. & Russell, V.A. Chronic Exposure to Light Reverses the Effect of Maternal Separation on Proteins in the Prefrontal Cortex. J Mol Neurosci 51, 835–843 (2013). https://doi.org/10.1007/s12031-013-0071-z

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