AGE-RELATED INCREASES IN GLIAL FIBRILLARY ACIDIC PROTEIN DO NOT SHOW PROPORTIONATE CHANGES IN TRANSCRIPTION RATES OR DNA METHYLATION IN THE CEREBRAL-CORTEX AND HIPPOCAMPUS OF MALE-RATS

Age-related increases in the expression of glial fibrillary acidic protein (GFAP) in many brain regions are observed in short- and long-lived mammals, Possible genomic mechanisms for the increase of GFAP mRNA and protein were studied in the hippocampus and cortex of male F344 rats and a longer-lived hybrid F-1 (F344 x Brown Norway), No age-related changes were found in the extent of cytosine methylation at 19 CpG sites in the 5'-upstream GFAP promoter and in exon 1, With the nuclear runon assay, no change was found in the transcription rate of GFAP in the cerebral cortex or hippocampus, Thus, age-related increases in GFAP are not associated with proportionate changes in transcription rates or DNA methylation, However, the transcription of glutamine synthetase was increased by about 60%. These findings contrast with age-related loss of bulk tissue DNA methylation and decreased transcription rates of other genes reported in non-neural tissues. (C) 1994 Wiley-Liss, Inc.