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

NEUROBIOLOGY OF AGING

卷:32

Article

Engler-Chiurazzi, Elizabeth^1,4  Tsang, Candy¹  Nonnenmacher, Sean¹  Liang, Winnie S.^3,4  Corneveaux, Jason J.^3,4  Prokai, Laszlo²  Huentelman, Matthew J.^3,4  Bimonte-Nelson, Heather A.^1,4 

[1] Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA

[2] Univ N Texas Hlth Sci Ctr, Ft Worth, TX 76107 USA

[3] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ 85004 USA

[4] Arizona Alzheimers Consortium, Phoenix, AZ USA

关键词: Premarin;    Estrogen;    Hormone replacement;    Working memory;    Spatial memory;    Neurotrophins;    Gene expression;   

DOI  :  10.1016/j.neurobiolaging.2009.09.005

来源: Elsevier

【 摘 要 】

Premarin (TM) 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 mu g 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:17 beta-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 17 beta-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. Published by Elsevier Inc.

【 授权许可】

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