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

Research output: Contribution to journalArticle

42 Scopus citations

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 36 μg 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.

Original languageEnglish
Pages (from-to)680-697
Number of pages18
JournalNeurobiology of Aging
Volume32
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Estrogen
  • Gene expression
  • Hormone replacement
  • Neurotrophins
  • Premarin
  • Spatial memory
  • Working memory

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    Engler-Chiurazzi, E., Tsang, C., Nonnenmacher, S., Liang, W. S., Corneveaux, J. J., Prokai, L., Huentelman, M. J., & Bimonte-Nelson, H. A. (2011). Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats. Neurobiology of Aging, 32(4), 680-697. https://doi.org/10.1016/j.neurobiolaging.2009.09.005