Affiliation:
1. Department of Cell and Molecular Physiology (Y.S.R., N.N.M., Y.W., T.R.P.), Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153
2. Department of Biological Sciences (W.C.J.C.), Kent State University, Kent, Ohio 44240
Abstract
Abstract
Menopause is characterized by the rapid age-related decline of circulating 17β-estradiol (E2) levels in women, which can sometimes result in cognitive disorders such as impaired memory and increased anxiety. Hormone therapy (HT) is a widely used treatment for the adverse effects associated with menopause; however, evidence suggests that HT administered to postmenopausal women age 65 years and over can lead to increased risks for cognitive disorders. We hypothesized that these age-related changes in E2 action are due to posttranscriptional gene regulation by microRNAs (miRNAs). miRNAs are a class of small noncoding RNAs that regulate gene expression by binding to the 3′-untranslated region of target mRNAs and subsequently target these transcripts for degradation. In the present study, 3- and 18-month-old female rats were oophorectomized (OVX) and treated 1 week after surgery with 2.5 μg E2 once per day for 3 days. Total RNA was isolated from the ventral and dorsal hippocampus, central amygdala, and paraventricular nucleus. Our results showed that E2 differentially altered miRNA levels in an age- and brain region-dependent manner. Multiple miRNA target prediction algorithms revealed putative target genes that are important for memory and stress regulation, such as BDNF, glucocorticoid receptor, and SIRT-1. Indeed, quantitative RT-PCR analyses of some of the predicted targets, such as SIRT1, showed that the mRNA expression levels were the inverse of the targeting miRNA, thereby confirming the prediction algorithms. Taken together, these data show that E2 regulates miRNA expression in an age- and E2-dependent manner, which we hypothesize results in differential gene expression and consequently altered neuronal function.
Reference82 articles.
1. Modulated microRNA expression during adult lifespan in Caenorhabditis elegans;Ibáñez-Ventoso;Aging Cell,2006
2. Novel microRNAs differentially expressed during aging in the mouse brain;Inukai;PLoS One,2012
3. Age-associated changes in expression of small, noncoding RNAs, including microRNAs, in C. elegans;Kato;RNA,2011
4. Up-regulation of key microRNAs, and inverse down-regulation of their predicted oxidative phosphorylation target genes, during aging in mouse brain;Li;Neurobiol Aging,2011
5. Genome-wide analysis of miRNA expression reveals a potential role for miR-144 in brain aging and spinocerebellar ataxia pathogenesis;Persengiev;Neurobiol Aging,2011
Cited by
55 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献