Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression

Iris Bertram, Hans Gert Bernstein, Uwe Lendeckel, Alicja Bukowska, Henrik Dobrowolny, Gerburg Keilhoff, Dimitrios Kanakis, Christian Mawrin, Hendrik Bielau, Peter Falkai, Bernhard Bogerts

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Abstract

In the central nervous system (CNS), neuregulin-1 (NRG-1) proteins function in neuronal migration, differentiation, and survival of oligodendrocytes. The NRG-1 gene codes for at least 15 different isoforms, which may be classified on the basis of their molecular structure. At least two different haplotypes of the NRG-1 gene may be associated with schizophrenia. An abnormal expression pattern of NRG-1 mRNA was found in the prefrontal cortex of schizophrenic patients in comparison to controls. We here show that the NRG-1α isoform is significantly reduced in white matter of the prefrontal cortex in schizophrenia but not in affective disorder. In the prefrontal gray matter, the density of NRG-1α expressing neurons was reduced in individuals with schizophrenia and in unipolar patients. We studied brains of 22 schizophrenics, 12 patients with affective disorders (7 unipolar and 5 bipolar), and 22 matched controls. NRG-1α immunoreactive material was detected with a polyclonal antiserum against the synthetic peptide from α-type EGF-like domain of human NRG. The demonstrated decreased number of NRG-1 immunoreactive neurons in the brains of schizophrenics and patients with unipolar depression points to an important role of this NRG-1α splice variant in neuropsychiatric disorders. Reduced NRG-1α protein concentrations were found in brains of schizophrenics after Western blot analysis. The diminished expression of NRG-1α strongly supports an early neurodevelopmental component to schizophrenia.

Original languageEnglish
Title of host publicationSignal Transduction Pathways, Part D
Subtitle of host publicationInflammatory Signaling Pathways and Neuropathology
Pages147-156
Number of pages10
Volume1096
DOIs
Publication statusPublished - Jan 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1096
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Adult human brain
  • Affective disorder
  • Immunohistochemistry
  • Morphometry
  • Neuregulin-1α
  • Prefrontal cortex
  • Schizophrenia

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    Bertram, I., Bernstein, H. G., Lendeckel, U., Bukowska, A., Dobrowolny, H., Keilhoff, G., Kanakis, D., Mawrin, C., Bielau, H., Falkai, P., & Bogerts, B. (2007). Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression. In Signal Transduction Pathways, Part D: Inflammatory Signaling Pathways and Neuropathology (Vol. 1096, pp. 147-156). (Annals of the New York Academy of Sciences; Vol. 1096). https://doi.org/10.1196/annals.1397.080