MicroRNAs in the Aging Female Brain: A Putative Mechanism for Age-Specific Estrogen Effects

作者: Yathindar S. Rao , Natasha N. Mott , Yanru Wang , Wilson C.J. Chung , Toni R. Pak

DOI: 10.1210/EN.2013-1230

关键词:

摘要: Menopause is characterized by the rapid age-related decline of circulating 17β-estradiol (E2) levels in women, which can sometimes result cognitive disorders such as impaired memory and increased anxiety. Hormone therapy (HT) a widely used treatment for adverse effects associated with menopause; however, evidence suggests that HT administered to postmenopausal women age 65 years over lead risks disorders. We hypothesized these changes E2 action are due posttranscriptional gene regulation microRNAs (miRNAs). miRNAs class small noncoding RNAs regulate expression binding 3′-untranslated region target mRNAs subsequently transcripts degradation. In present study, 3- 18-month-old female rats were oophorectomized (OVX) treated 1 week after surgery 2.5 μg once per day 3 days. Total RNA was isolated from ventral dorsal hippocampus, central amygdala, paraventricular nucleus. Our results showed differentially altered miRNA an age- brain region-dependent manner. Multiple prediction algorithms revealed putative genes important stress regulation, BDNF, glucocorticoid receptor, SIRT-1. Indeed, quantitative RT-PCR analyses some predicted targets, SIRT1, mRNA inverse targeting miRNA, thereby confirming algorithms. Taken together, data show regulates E2-dependent manner, we hypothesize differential consequently neuronal function.

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