title: Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression.
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-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. 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-1alpha splice variant in neuropsychiatric disorders. Reduced NRG-1alpha protein concentrations were found in brains of schizophrenics after Western blot analysis. The diminished expression of NRG-1alpha strongly supports an early neurodevelopmental component to schizophrenia.
authors.affiliation: Exp. Psychiatry Lab., University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Bertram
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Uwe
authors.initials: U
authors.lastname: Lendeckel
authors.forename: Alicja
authors.initials: A
authors.lastname: Bukowska
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kanakis
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bielau
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
mesh_terms: D000328:Adult; D002465:Cell Movement; D003866:Depressive Disorder / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000096:biosynthesis*; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology*; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D020890:Neuregulin-1