NEUROTROPHIC FACTOR GENE-EXPRESSION IN ASTROCYTES DURING DEVELOPMENT AND FOLLOWING INJURY

Astrocyte cultures were utilized to examine regulation of the expression of several trophic factor genes. Regulation by the beta-adrenergic receptor was demonstrated by exposure of striatal and cortical astrocytes to isoproterenol, which resulted in increased content of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor, and proenkephalin (PE), as well as NGF and Met-enkephalin. Developmental regulation was analyzed by preparing cortical astrocytes from animals of four different ages-embryonic day 20, postnatal days 3 and 8, and adult. Because both the PE and NGF genes showed developmental downregulation, we asked whether we could prepare reactive astrocytes from lesioned adult brain and see expression turned back on. Astrocytes prepared from 6-hydroxydopamine-lesioned rat striatum or MPTP-lesioned mouse striatum contained increased GFAP and NGF mRNA. Comparable changes in GFAP and NGF could be achieved by treatment of control cultures with interferon-gamma or interleukin-1 beta. These results suggest that locus coeruleus neurons could control astrocyte synthesis of neurotrophic factors through release of norepinephrine, but that in injured brain other factors, such as cytokines, may become equally important.