Oxygen restriction of neonate rats elevates neuregulin-1α isoform levels: Possible relationship to schizophrenia

Neuregulin-1 (NRG-1), a replicated gene in schizophrenia-association studies, exhibits six mRNA-types and two types of the EGF-like domain, α and β. The β-isoform was extensivly studied, less is known about the extent and specific localization of adult brain NRG-1α. NRG-1α protein levels were reported reduced in postmortem prefrontal-cortex of schizophrenia patients. NRG-1 type I mRNA levels were found higher in postmortem brain in schizophrenia. In an attempt to decipher between a genetic or environmental involvement in the differences in NRG-1 levels in postmortem brain in schizophrenia, and since obstetric complications were suggested non-genetic risk-factors of schizophrenia, we studied the effect of perinatal hypoxia in rats on brain NRG-1α protein levels. Seven-day-old rats were exposed to hypoxia versus air. Frontal-cortex levels of NRG-1α isoform were quantified at adulthood by Western blotting. Frontal-cortex NRG-1α was 32% elevated in hypoxia-exposed rats. The data support the role of non-genetic factors, e.g. oxygen restriction, in the expression of genes associated with schizophrenia.