INCREASED EXPRESSION OF THE NEUROFIBROMATOSIS-1 (NF1) GENE-PRODUCT, NEUROFIBROMIN, IN ASTROCYTES IN RESPONSE TO CEREBRAL-ISCHEMIA

Tumor suppressor genes encode proteins involved in growth regulation i n differentiating and proliferating cells, previous work from our labo ratory has demonstrated that the neurofibromatosis 1 (NF1) tumor suppr essor gene is dramatically upregulated in astrocytes stimulated with d ibutyryl cyclic AMP and proinflammatory cytokines, To explore the poss ibility that the NF1 gene product, neurofibromin, plays a role in the reactive gliosis seen in response to cerebral ischemia, expression of NF1 was examined in both focal and global models of rat cerebral ische mia. In this report, we demonstrate the increased expression of both n eurofibromin and glial fibrillary acidic protein (GFAP) in astrocytes surrounding areas of focal ischemia, Similar increases in neurofibromi n and GFAP immunoreactivity were also observed in reactive astrocytes in the hippocampal region in a global model of ischemia, These results suggest a novel role for the NF1 tumor suppressor gene in growth regu latory pathways involved in cellular remodeling and in response to inj ury. (C) 1996 Wiley-Liss, Inc.