BRAIN NEURONS AND GLIAL-CELLS EXPRESS NEU DIFFERENTIATION FACTOR HEREGULIN - A SURVIVAL FACTOR FOR ASTROCYTES

Neu differentiation factor (NDF, also called heregulin) was isolated f rom mesenchymal cells on the basis of its ability to elevate phosphory lation of ErbB proteins. Earlier in situ hybridization analysis showed that NDF was transcribed predominantly in the central nervous system during embryonic development. To gain insights into the role of NDF in brain we analyzed its distribution by inmunohistochemistry and in sit u hybridization. Late-gestation (day 17) rat embryos displayed high ND F immunoreactivity in both motor (e.g., putamen) and limbic (e.g., sep tum) regions. Lower levels of the factor were exhibited by adult brain , except for the cerebellum, where NDF expression was increased postna tally. Both neurons and glial cells were identified by immunohistochem istry as NDF-producing cells (e.g., pyramidal neurons in the cerebral cortex and glial cells in the corpus callosum). By establishment of pr imary cultures of rat brain cells we confirmed that NDF was expressed in neurons as well as in astrocytes. In addition, by using such primar y cultures we observed that NDF treatment exerted only a limited mitog enic effect, which was accompanied by significant acceleration of astr ocyte maturation. Furthermore, long-term incubation with the factor sp ecifically protected astrocytes from apoptosis, implying that NDF func tions in brain as a survival and maturation factor for astrocytes.