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Increased Density of Prohibitin-Immunoreactive Oligodendrocytes in the Dorsolateral Prefrontal White Matter of Subjects with Schizophrenia Suggests Extraneuronal Roles for the Protein in the Disease

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Abstract

Prohibitin has previously been implicated in the synaptic pathology of schizophrenia. The recently discovered abundant expression of prohibitin in human prefrontal oligodendrocytes raises the issue, whether this protein might also be part of the well-known white matter abnormalities in schizophrenia. Hence, post-mortem brains of ten patients with schizophrenia and ten matched control cases were investigated. Using a direct, 3D-counting technique we morphometrically analyzed the number and density of prohibitin-immunoreactive oligodendroglial cells in the left and right dorsolateral, anterior cingulate, and orbitofrontal cortex white matter. Additionally, we studied the prohibitin expression in different neuronal and non-neuronal cell populations in rat cell cultures. We could confirm the strong expression of prohibitin in oligodendrocytes. Intracellularly, the protein was localized to mitochondria and some cell nuclei. In schizophrenia, the numerical density of prohibitin-expressing oligodendrocytes was significantly increased in the right dorsolateral white matter area. Taking into consideration the dual intracellular localization of prohibitin in oligodendrocyte mitochondria and cell nuclei, one may suggest an involvement of the protein in mitochondrial dysfunction and/or cycle abnormalities in schizophrenia.

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Abbreviations

3D:

Three dimensional

ACC:

Anterior cingulate cortex

CA:

California

DAPI:

4′,6′-diamidine-2′-phenylindol-dihydrochloride

DLPFC:

Dorsolateral prefrontal cortex

DMEM:

Dulbecco’s Modified Eagle Medium

DSM:

Diagnostic and Statistical Manual of Mental Disorders

FCS:

Fetal calf serum

GFAP:

Glial fibrillary acidic protein

iNOS:

Inducible nitric oxide synthase

MAP2:

Microtubule-associated protein 2

MBP:

Myelin basic protein

OFC:

Orbitofrontal cortex

OL:

Oligodendrocyte(s)/oligodendroglia

Olig2:

Oligodendrocyte transcription factor 2

OLN-93:

Rat oligodendroglia cell line 93

PBS:

Phosphate buffered saline

PFA:

Paraformaldehyde fixation buffer

PSD:

Postsynaptic density

SD:

Standard deviation

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Acknowledgments

The authors would like to kindly thank Prof. Dr. C. Richter-Landsberg (University of Oldenburg, Germany) for providing the OLN-93 cell line.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry, University of Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany

    Hans-Gert Bernstein, Diana Dürrschmidt, Henrik Dobrowolny, Johann Steiner & Bernhard Bogerts

  2. SL Mol. Biol. Techniques, Leibniz Institute for Neurobiology, Magdeburg, Germany

    Karl-Heinz Smalla

  3. Institute for Biochemistry and Cell Biology, University of Magdeburg, Magdeburg, Germany

    Gerburg Keilhoff

  4. Department of Psychiatry, University of Munich, Munich, Germany

    Andrea Schmitt

  5. RG Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany

    Michael R. Kreutz

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  1. Hans-Gert Bernstein
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  2. Karl-Heinz Smalla
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Correspondence to Hans-Gert Bernstein.

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Bernstein, HG., Smalla, KH., Dürrschmidt, D. et al. Increased Density of Prohibitin-Immunoreactive Oligodendrocytes in the Dorsolateral Prefrontal White Matter of Subjects with Schizophrenia Suggests Extraneuronal Roles for the Protein in the Disease. Neuromol Med 14, 270–280 (2012). https://doi.org/10.1007/s12017-012-8185-y

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