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Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia

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Journal of Neurocytology

Abstract

There is growing interest in the cerebellum as a site of neuropathological changes in schizophrenia. Reports showing that schizophrenics have higher nitric oxide synthase (NOS) activity and MAPKinase levels in the vermis, point to possible aberrations in the cerebellar signal transduction of schizophrenics. It has been speculated that Ca2+-dependent extracellular to intracellular signal transduction may be disrupted in the cerebellum of schizophrenics. We decided to test this hypothesis by studying the nitrergic system and markers of the Ca2+-triggered signal cascade in the cerebellum of schizophrenics, depressives and controls. The cellular distribution of two calcium sensor proteins (VILIP-1 and VILIP-3) and of neuronal NOS immunoreactivity was studied morphometrically in the flocculonodulus, the inferior vermis and the dentate nucleus of 9 schizophrenics, 7 depressive patients and 9 matched controls. In comparison to controls and depressed patients there were fewer Nissl-stained neurons in the dentate nucleus of schizophrenics. The number of NOS-expressing Purkinje neurons was however strongly increased. In the flocculonodulus and the vermis no differences between the groups were found with regard to the density of Nissl-stained Purkinje cells. The number of NOS-expressing Purkinje neurons was increased in schizophrenics, however. No differences between schizophrenics, depressives and controls were found in the number of VILIP-1 immunoreactive dentate nucleus neurons and VILIP-3 immunoreactive vermal and flocculonodular Purkinje cells. Our data provide further histochemical evidence in favor of structural abnormalities in discrete cerebellar regions of schizophrenics. They confirm and extend earlier reports of increased cerebellar NOS immunoreactivity in schizophrenia and point to possible neurodevelopmental disturbances. Our failure to show an altered expression of two calcium sensor proteins possibly points to a less important role of calcium signaling in cerebellar pathology of the disease.

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Authors and Affiliations

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

    Hans-Gert Bernstein, Dieter Krell, Bruno Baumann, Silvia Diekmann, Peter Danos & Bernhard Bogerts

  2. Department of Neurochemistry, Leibniz Institute for Neurobiology, Magdeburg, Germany;

    Karl-Heinz Braunewell & Eckart D. Gundelfinger

  3. Signal Transduction Research Group, Neuroscience Research Center of the Charité, Berlin, Germany

    Karl-Heinz Braunewell

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  1. Hans-Gert Bernstein
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  2. Dieter Krell
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  3. Karl-Heinz Braunewell
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  4. Bruno Baumann
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  5. Eckart D. Gundelfinger
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Correspondence to Hans-Gert Bernstein.

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Bernstein, HG., Krell, D., Braunewell, KH. et al. Increased number of nitric oxide synthase immunoreactive Purkinje cells and dentate nucleus neurons in schizophrenia. J Neurocytol 30, 661–670 (2001). https://doi.org/10.1023/A:1016520932139

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