ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system

The neuregulin (NRG) family of growth and differentiation factors and their erbB receptors contribute importantly to the development of the nervous sy stem, but their distribution and function in the adult brain are poorly und erstood. The present study showed that erbB2, erbB3, and erbB4, transcripts and protein are distributed throughout all areas of adult rat; brain. Thes e three receptors were differentially expressed in neurons and glia. Some n eurons expressed only a subset of erbB kinases, whereas other neurons expre ssed all three erbB receptors but sequestered each of these polypeptides in to distinct cellular compartments. In synapse-rich regions, erbB immunoreac tivity appeared as punctate-, axon-, and/or dendrite-associated staining, s uggesting that NRGs are involved in the formation and maintenance of synaps es in adult brain. ErbB labeling also was present in neuronal some, indicat ing that NRGs act at sites in addition to the synapse. Glia in adult brain also differentially expressed erbB3 and erbB4. Approximately half of the er bB3 labeling in white matter was associated with S100 beta+/glial fibrillar y acidic protein negative macroglia (i.e., oligodendrocytes or glial fibril lary acidic protein negative astrocytes). In contrast, macroglia in gray ma tter did not express erbBS. The remaining erbBS immunoreactivity in white m atter and erbB3 glial staining seemed to be associated with microglia. Thes e results showed that erbB receptors are expressed widely in adult rat brai n and that each erbB receptor subtype has a distinct distribution. The diff erential distributions of erbB receptors in neurons and glia and the known functional differences between these kinases suggest that NRGs have distinc t effects on these cells. The continued expression of NRGs and their erbB r eceptors in mature brain also implies that these molecules perform importan t functions in the brain throughout life. (C) 2001 Wiley-Liss, Inc.