Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 5
Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal
cortex in schizophrenia but not in affective disorders
Iris Bertram1, Hans-Gert Bernstein1, Uwe Lendeckel2, Alicja Bukowska2, Henrik
Dobrowolny1, Gerburg Keilhoff3, Christian Mawrin4 ,Peter Falkai5 and Bernhard
Bogerts1
1 Exp. Psychiatry Lab., Psychiatry, University of Magdeburg, Magdeburg, Germany;
2 Exp. Int. Med. lab., Internal Medicine, University of Magdeburg, Magdeburg,
Germany; 3 Cell Tissue Lab., Med. Neurobiology, University of Magdeburg,
Magdeburg, Germany; 4 Exp. Neuropathology Lab., Neuropathology, University of
Magdeburg, Magdeburg, Germany; 5 Department of Psychiatry, University of
Saarland, Homburg; E-mail: Hans-Gert.Bernstein@medizin.uni-magdeburg.de
In the 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-1alpha isoform is significantly reduced in white matter
of the prefrontal cortex in schizophrenia but not in affective disorders. Brains were obtained
from pathologists in accordance rules outlined by German law and the local ethics
commission. We studied brains of 22 schizophrenics, 12 patients with affective disorders (7
unipolar and 5 bipolar) and 22 matched controls. NRG-1alpha immunoreactive material was
detected with a polyclonal antiserum against the synthetic peptide from alpha-type EGF-like
domain of human neuregulin (Ab-3, Neomarkers). When stereologically analysing the
number of NRG-1alpha expressing neurons we found a statistically significant reduction of
these cells in the white, but not in the gray, cortical matter in schizophrenia but not in
depression. The demonstrated decreased number of NRG-1alpha immunoreactive neurons in
brains of schizophrenics point to an important role of this NRG-1 splice variant in
neuropsychiatric disorders. The diminished expression of NRG-1alpha in interstitial white
matter neurons strongly supports an early neurodevelopmental component to schizophrenia.
Supported by NBL-3 of the Ministry of Research of Germany, and Stanley Foundation.
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