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雄性大鼠大脑皮层和海马体中,与年龄相关的胶质纤维酸性蛋白增加并未表现出转录速率或DNA甲基化的相应变化。

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.

作者信息

Laping N J, Teter B, Anderson C P, Osterburg H H, O'Callaghan J P, Johnson S A, Finch C E

机构信息

Renal Pharmacology Department, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.

出版信息

J Neurosci Res. 1994 Dec 15;39(6):710-7. doi: 10.1002/jnr.490390612.

DOI:10.1002/jnr.490390612
PMID:7897706
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.

摘要

在短期和长期存活的哺乳动物中,均可观察到许多脑区中与年龄相关的胶质纤维酸性蛋白(GFAP)表达增加。研究了雄性F344大鼠和寿命更长的杂种F1(F344× 褐家鼠)的海马体和皮质中GFAP mRNA和蛋白质增加的可能基因组机制。在GFAP启动子5'上游和外显子1的19个CpG位点的胞嘧啶甲基化程度上未发现与年龄相关的变化。通过核转录分析,未发现大脑皮质或海马体中GFAP转录率有变化。因此,GFAP与年龄相关的增加与转录率或DNA甲基化的相应变化无关。然而,谷氨酰胺合成酶的转录增加了约60%。这些发现与非神经组织中报道的与年龄相关的大量组织DNA甲基化丧失和其他基因转录率降低形成对比。

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