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MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects.

ABSTRACT: Menopause is characterized by the rapid age-related decline of circulating 17?-estradiol (E(2)) 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 E(2) 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 ?g E(2) 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 E(2) 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 E(2) regulates miRNA expression in an age- and E(2)-dependent manner, which we hypothesize results in differential gene expression and consequently altered neuronal function.

SUBMITTER: Rao YS

PROVIDER: S-EPMC3713211 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects.

Rao Yathindar S YS Mott Natasha N NN Wang Yanru Y Chung Wilson C J WC Pak Toni R TR

Endocrinology 20130529 8

Menopause is characterized by the rapid age-related decline of circulating 17β-estradiol (E(2)) 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 chang ...[more]

PMID: 23720423

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Project description:Introduction: Novel post-processing methods allow not only for assessment of brain volumetry or cortical thickness based on magnetic resonance imaging (MRI) but also for more detailed analysis of cortical shape and complexity using parameters such as sulcal depth, gyrification index, or fractal dimension. The aim of this study was to analyze changes in brain volumetry and other cortical indices during aging in men and women. Material and Methods: Material consisted of 697 healthy volunteers (aged 38-80 years; M/F, 264/443) who underwent brain MRI using a 1.5-T scanner. Voxel-based volumetry of total gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was performed followed by assessment of cortical parameters [cortical thickness (CT), sulcal depth (SD), gyrification index (GI), and fractal dimension (FD)] in 150 atlas locations using surface-based morphometry with a region-based approach. All parameters were compared among seven age groups (grouped every 5 years) separately for men and women. Additionally, percentile curves for men and women were provided for total volumes of GM, WM, and CSF. Results: In men and women, a decrease in GM and WM volumes and an increase in CSF volume seem to progress slowly since the age of 45. In men, significant GM and WM loss as well as CSF increase start above 55 years of age, while in women, significant GM loss starts above 50 and significant WM loss as well as CSF increase above 60. CT was found to significantly decrease with aging in 39% of locations in women and in 36% of locations in men, SD was found to increase in 13.5% of locations in women and in 1.3% of locations in men, GI was decreased in 3.4% of locations in women and in 2.0% of locations in men, and FD was changed in 2.7% of locations in women compared to 2.0% in men. Conclusions: Male and female brains start aging at the similar age of 45. Compared to men, in women, the cortex is affected earlier and in the more complex pattern regarding not only cortical loss but also other alterations within the cortical shape, with relatively longer sparing of WM volume.

Dataset Information

MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects.

Publications

MicroRNAs in the aging female brain: a putative mechanism for age-specific estrogen effects.

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