Expression of ErbB4 in substantia nigra dopamine neurons of monkeys and humans

Abnormal neuregulin-1 signaling through its receptor (ErbB4) might be associated with schizophrenia, although their neuropathological contribution remains controversial. To assess the role of neuregulin-1 in the dopamine hypothesis of schizophrenia, we used in situ hybridization and immunoblotting to investigate the cellular distribution of ErbB4 mRNA in the substantia nigra of Japanese monkeys (Macaca fuscata) and human postmortem brains. In both monkeys and humans, significant signal for ErbB4 mRNA was detected in substantia nigra dopamine neurons, which were identified by melanin deposits. The expression of ErbB4 mRNA in nigral dopamine neurons was confirmed with an independent RNA probe, as well as with combined tyrosine hydroxylase immunostaining. Immunoblotting appeared to support the observation of in situ hybridization. Immunoreactivity for ErbB4 protein was much more enriched in substantia nigra pars compacta containing dopamine neurons than in neighboring substantia nigra pars reticulata. These observations suggest that ErbB4 is expressed in the dopaminergic neurons of primate substantia nigra and ErbB4 abnormality might contribute to the dopaminergic pathology associated with schizophrenia or other brain diseases.