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Neurobiology of aging
Apr, 2011;32 (4): 680-97.

Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats.

Elizabeth Engler-Chiurazzi, Candy Tsang, Sean Nonnenmacher, Winnie S Liang, Jason J Corneveaux, Laszlo Prokai, Matthew J Huentelman, Heather A Bimonte-Nelson
Author Information
  1. Elizabeth Engler-Chiurazzi: Department of Psychology, Arizona State University, Tempe, AZ 85287, USA. Elizabeth.engler-chiurazzi@asu.edu
PMID: 19883953 DOI: 10.1016/j.neurobiolaging.2009.09.005

Abstract

Premarin™ is the most commonly prescribed estrogenic component of hormone therapy, given since 1942. The current study is the first examining cognitive effects of tonic Premarin treatment in an animal model. Middle-aged ovariectomized (Ovx) rats received vehicle or one of three doses of Premarin (12, 24 or 36μg daily). Rats were tested on a spatial working and reference memory maze battery. Both medium- and high-dose Premarin enhanced memory retention, while low-dose Premarin impaired learning and memory retention. Correlations with serum hormone levels showed that as the ratio of estrone:17β-estradiol increased, animals tended to show better working memory performance. Taken together with the dissociation of dose-specific estrogenic profiles, results suggest that higher levels of estrone, in the presence of 17β-estradiol concentrations higher than that of Ovx levels, may be beneficial for memory. Moreover, Premarin exerted dose and brain-region specific effects on BDNF and NGF protein levels, with most marked changes in cingulate and perirhinal cortices. Hippocampal gene expression profiling demonstrated significant Premarin-induced transcriptional changes in genes linked to plasticity and cognition. These findings indicate that Premarin can impact memory and the brain, and that dosing should be recognized as a clinically relevant factor possibly affecting the direction and efficacy of cognitive outcome.

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Grants

  1. R01 AG028084/NIA NIH HHS
  2. R01 AG028084-02/NIA NIH HHS
  3. AG028084/NIA NIH HHS

MeSH Term

Animals
Brain-Derived Neurotrophic Factor
Cerebral Cortex
Dose-Response Relationship, Drug
Estrogens
Estrogens, Conjugated (USP)
Female
Gene Expression
Hippocampus
Maze Learning
Memory
Nerve Growth Factor
Ovariectomy
Rats
Rats, Inbred F344
Space Perception
Vaginal Smears

Chemicals

Brain-Derived Neurotrophic Factor
Estrogens
Estrogens, Conjugated (USP)
Nerve Growth Factor
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Word Cloud

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