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

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Abstract
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 F1 (F344 × 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.