title: 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.
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 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.
authors.affiliation: Renal Pharmacology Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
authors.forename: N J
authors.initials: NJ
authors.lastname: Laping
authors.forename: B
authors.initials: B
authors.lastname: Teter
authors.forename: C P
authors.initials: CP
authors.lastname: Anderson
authors.forename: H H
authors.initials: HH
authors.lastname: Osterburg
authors.forename: J P
authors.initials: JP
authors.lastname: O'Callaghan
authors.forename: S A
authors.initials: SA
authors.lastname: Johnson
authors.forename: C E
authors.initials: CE
authors.lastname: Finch
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics*; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008745:Methylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D015342:DNA Probes; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D004247:DNA