MK4MDD

Study Report

Reference
CitationBertram, 2007 PubMed
Full InfoBertram, I., Bernstein, H.G., Lendeckel, U., Bukowska, A., Dobrowolny, H., Keilhoff, G., Kanakis, D., Mawrin, C., Bielau, H., Falkai, P. et al. (2007) Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression. Ann N Y Acad Sci, 1096, 147-156.

Study
Hypothesis or Background 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.
Sample Information22 schizophrenics, 12 patients with affective disorders (7 unipolar and 5 bipolar), and 22 matched controls
Method DetailWe here show that the NRG-1alpha 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-1alpha 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-1alpha immunoreactive material was detected with a polyclonal antiserum against the synthetic peptide from alpha-type EGF-like domain of human NRG.
Method Keywordspostmortem study; immunocytochemical analysis; immunoblotting; Q-PCR
ResultThe 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-1alpha splice variant in neuropsychiatric disorders. Reduced NRG-1alpha protein concentrations were found in brains of schizophrenics after Western blot analysis.
ConclusionsThe diminished expression of NRG-1alpha strongly supports an early neurodevelopmental component to schizophrenia.

Relationships reported by Bertram, 2007