Strongly reduced number of neuregulin–1- alpha expressing prefrontal gray and white matter neurons in schizophrenia

Numerous studies have reported linkage between the neuregulin 1 (NRG–1) gene and schizophrenia. The NRG–1 gene code for at least 15 different isoforms. All isoforms contain either an alpha or a beta epidermal growth factor-like domain, which interacts with the erbB-tyrosine kinases receptors to activate them. While brain-associated NRG1 beta forms have extensively been investigated, much less is known about the occurrence and distribution of NRG–1 alpha forms in the human CNS. Studying the regional distriution of NRG 1-alpha containing neurons and the amount of protein in 10 schizophrenics and 10 matched controls by immunohistochemistry, Western blot analysis and PCR we show that NRG 1-alpha is widely distributed in neurons of human brain and altered in schizophrenia. In the human brain this NRG 1 isoform is restricted to a few cortical neurons and some white matter interstitial neurons. In comparison to controls less protein was found in brains of schizophrenics. The number of prefrontal NRG 1-alpha expressing neurons was significantly reduced in gray and white matter prefrontal cortex. We conclude the NRG 1-alpha plays a role in human brain development and is involved in the pathophysiology of schizophrenia. A possible effect of medication on the NRG 1-alpha expression is currently under investigation. Financial supprt: Program NBL–3 of BMVF of Germany and Stanley Foundation.