Unknown

Dataset Information

0

A comparative evaluation of treatments with 17?-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease.


ABSTRACT: Estrogens are neuroprotective and, thus, potentially useful for the therapy of Alzheimer's disease; however, clinical use of hormone therapy remains controversial due to adverse peripheral effects. The goal of this study was to investigate the benefits of treatment with 10?,17?-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective prodrug of 17?-estradiol, in comparison with the parent hormone using APPswe/PS1dE9 double transgenic mice to model the pathology of the disease. Ovariectomized and intact females were continuously treated with vehicle, 17?-estradiol, or DHED via subcutaneous osmotic pumps from 6 to 8months of age. We confirmed that this prolonged treatment with DHED did not stimulate uterine tissue, whereas 17?-estradiol treatment increased uterine weight. Amyloid precursor protein decreased in both treatment groups of intact, but not in ovariectomized double transgenic females in which ovariectomy already decreased the expression of this protein significantly. However, reduced brain amyloid-? peptide levels could be observed for both treatments. Consequently, double-transgenic ovariectomized and intact mice had higher cognitive performance compared to untreated control animals in response to both estradiol and DHED administrations. Overall, the tested brain-selective 17?-estradiol prodrug proved to be an effective early-stage intervention in an Alzheimer's disease-relevant mouse model without showing systemic impact and, thus, warrants further evaluation as a potential therapeutic candidate.

SUBMITTER: Tschiffely AE 

PROVIDER: S-EPMC4950979 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

A comparative evaluation of treatments with 17β-estradiol and its brain-selective prodrug in a double-transgenic mouse model of Alzheimer's disease.

Tschiffely Anna E AE   Schuh Rosemary A RA   Prokai-Tatrai Katalin K   Prokai Laszlo L   Ottinger Mary Ann MA  

Hormones and behavior 20160519


Estrogens are neuroprotective and, thus, potentially useful for the therapy of Alzheimer's disease; however, clinical use of hormone therapy remains controversial due to adverse peripheral effects. The goal of this study was to investigate the benefits of treatment with 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), a brain-selective prodrug of 17β-estradiol, in comparison with the parent hormone using APPswe/PS1dE9 double transgenic mice to model the pathology of the disease. Ovariectomized and  ...[more]

Similar Datasets

| S-EPMC7260153 | biostudies-literature
| S-EPMC6429175 | biostudies-literature
| S-EPMC5560305 | biostudies-other
| S-EPMC5686603 | biostudies-literature
| S-EPMC3954939 | biostudies-literature
| S-EPMC6159732 | biostudies-literature
| S-EPMC3249832 | biostudies-literature
| S-EPMC6707591 | biostudies-literature
| S-EPMC4879824 | biostudies-literature
| S-EPMC5733185 | biostudies-literature