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 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.
Laping
N J
NJ
Renal Pharmacology Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Teter
B
B
Anderson
C P
CP
Osterburg
H H
HH
O'Callaghan
J P
JP
Johnson
S A
SA
Finch
C E
CE
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*
D015342:DNA Probes; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D004247:DNA