title: Astrocyte gene expression in Creutzfeldt-Jakob disease.
abstract: Gliosis (hyperplasia and hypertrophy of astrocytes), the fundamental response of the central nervous system to tissue destruction, typically becomes apparent only several weeks after injury. The biochemical hallmark of this response is a marked accumulation of the specific astrocyte intermediate filament glial fibrillary acidic protein (GFAP). To date despite its importance, the mechanisms of GFAP gene regulation have not been studied in any developmental or pathological system to our knowledge, and the molecular signals for GFAP mRNA and protein accumulation are not defined. In Creutzfeldt-Jakob disease, a progressive dementing illness caused by an "unconventional agent," we find steadily increasing elevations of GFAP mRNA throughout the later stages of disease, using two independent GFAP cDNA clones, representing the entire insert or the 3'-noncoding region (pScr-1). The accumulation of GFAP, assessed immunocytochemically, follows GFAP mRNA elevation. A 5-fold stimulation of GFAP gene expression precedes the development of florid histologic lesions in the cerebrum, and in the cerebellum 5- to 6-fold increases occurred with no detectable spongiform changes at any time during disease. Therefore, these GFAP changes cannot be simply a response to neuronal damage. These effects are directly or indirectly caused by high local concentrations of agent and possibly involve a humoral factor.
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics*; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D004262:DNA Restriction Enzymes