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Proteomic Investigation of the Ventral Rat Hippocampus Links DRP-2 to Escitalopram Treatment Resistance and SNAP to Stress Resilience in the Chronic Mild Stress Model of Depression

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Abstract

The development of depression as well as recovery from depression is most likely accompanied by a change in protein expression profiles. The purpose of the present study was to quantitatively investigate global protein expression differences independent of any hypothesis describing depression etiology and recovery. Thus two-dimensional differential in-gel electrophoresis was employed to compare the ventral hippocampal proteomes between different treatment groups in the chronic mild stress (CMS) model of depression. The CMS paradigm induces anhedonic behaviour, which is a major symptom of depression, by exposing rats to a series of mild stressors for 7 weeks, with antidepressant treatment during the last 4 weeks. In the CMS model, animals were split into six different groups at the end of treatment; unchallenged control escitalopram (n =  12), unchallenged control vehicle (n = 12), CMS vehicle (n = 12), CMS escitalopram responders (n  =  11), CMS escitalopram non-responders (n  =  13) and CMS resilient (stress resistant) (n  =  12). Protein levels in the ventral rat hippocampus were compared between the groups to provide putative markers of anhedonia, escitalopram resistance, and stress resilience. Twenty-eight candidate protein spots were selected, of which 13 were successfully identified using tandem mass spectrometry. DRP-2 (dihydropyrimidinase-related protein-2) was a potential marker for escitalopram resistance, whereas α-SNAP and β-SNAP were associated with stress resilience. Furthermore, several molecular chaperones and cytoskeleton organisers were identified as being differentially expressed. Our data indicate that neuronal adaptation is an essential element of depression etiology and recovery, suggesting the involvement of cellular plasticity in the underlying molecular mechanism.

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Acknowledgements

We thank Thomas Thykær Andersen for help with the hierarchical clustering analysis and Leif Schauser for help with the statistical analysis. This work was supported by the Lundbeck foundation and the Danish Medical Research Council.

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Authors and Affiliations

  1. Center for Basic Psychiatric Research, Aarhus Psychiatric University Hospital, Skovagervej 2, 8240, Risskov, Denmark

    Christina F. Bisgaard, Magdalena N. Jayatissa & Ove Wiborg

  2. Center for Insoluble Protein Structure (inSPIN), Department of Molecular Biology, Science Park, University of Aarhus, Aarhus, Denmark

    Jan J. Enghild

  3. H. Lundbeck A/S, Lundbeck Research US, 215 College Road, Paramus, NJ, 07652, USA

    Connie Sanchéz & Roman Artemychyn

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  1. Christina F. Bisgaard
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Bisgaard, C.F., Jayatissa, M.N., Enghild, J.J. et al. Proteomic Investigation of the Ventral Rat Hippocampus Links DRP-2 to Escitalopram Treatment Resistance and SNAP to Stress Resilience in the Chronic Mild Stress Model of Depression. J Mol Neurosci 32, 132–144 (2007). https://doi.org/10.1007/s12031-007-0025-4

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