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A comparison of the synaptic proteome in human chronic schizophrenia and rat ketamine psychosis suggest that prohibitin is involved in the synaptic pathology of schizophrenia

Molecular Psychiatry volume 13, pages 878–896 (2008)Cite this article

Abstract

Many studies in recent years suggest that schizophrenia is a synaptic disease that crucially involves a hypofunction of N-methyl-D-aspartate receptor-mediated signaling. However, at present it is unclear how these pathological processes are reflected in the protein content of the synapse. We have employed two-dimensional gel electrophoresis in conjunction with mass spectrometry to characterize and compare the synaptic proteomes of the human left dorsolateral prefrontal cortex in chronic schizophrenia and of the cerebral cortex of rats treated subchronically with ketamine. We found consistent changes in the synaptic proteomes of human schizophrenics and in rats with induced ketamine psychosis compared to controls. However, commonly regulated proteins between both groups were very limited and only prohibitin was found upregulated in both chronic schizophrenia and the rat ketamine model. Prohibitin, however, could be a new potential marker for the synaptic pathology of schizophrenia and might be causally involved in the disease process.

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Acknowledgements

This study was supported by grants from the BMBF (01GZ0307/ 01GA0505), DFG (SFB 779 TP B8+B9), LSA (N1/TP4, N2 TP5), Schram Foundation, Leibniz Society (Pakt fĂĽr Forschung) and Fonds der Chemischen Industrie to EDG and MRK, and Center for Medical Systems Biology (CMSB) to KWL and ABS. JS is supported by a stipend from the DFG graduate program (GRK 1167). We gratefully acknowledge the professional technical assistance of C Borutzki, H Dobrowolny, S Funke, M Marunde and K Pohlmann.

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Authors and Affiliations

  1. Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, Magdeburg, Germany

    K-H Smalla

  2. Project Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany

    M Mikhaylova, J Sahin & M R Kreutz

  3. Department of Psychiatry, Medical Faculty, Otto-von Guericke University, Magdeburg, Germany

    H-G Bernstein & B Bogerts

  4. Department of Psychiatry, Medical Faculty, Georg-August University Göttingen, Germany

    A Schmitt

  5. Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, The Netherlands

    R van der Schors, A B Smit & K W Li

  6. Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany

    E D Gundelfinger

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  1. K-H Smalla
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Smalla, KH., Mikhaylova, M., Sahin, J. et al. A comparison of the synaptic proteome in human chronic schizophrenia and rat ketamine psychosis suggest that prohibitin is involved in the synaptic pathology of schizophrenia. Mol Psychiatry 13, 878–896 (2008). https://doi.org/10.1038/mp.2008.60

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