Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression.
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.
Bertram
Iris
I
Exp. Psychiatry Lab., University of Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Bernstein
Hans-Gert
HG
Lendeckel
Uwe
U
Bukowska
Alicja
A
Dobrowolny
Henrik
H
Keilhoff
Gerburg
G
Kanakis
Dimitrios
D
Mawrin
Christian
C
Bielau
Hendrik
H
Falkai
Peter
P
Bogerts
Bernhard
B
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
D020890:Neuregulin-1