Tonic Premarin dose-dependently enhances memory, affects neurotrophin protein levels and alters gene expression in middle-aged rats.
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.
Engler-Chiurazzi
Elizabeth
E
Department of Psychology, Arizona State University, Tempe, AZ 85287, USA. Elizabeth.engler-chiurazzi@asu.edu
Tsang
Candy
C
Nonnenmacher
Sean
S
Liang
Winnie S
WS
Corneveaux
Jason J
JJ
Prokai
Laszlo
L
Huentelman
Matthew J
MJ
Bimonte-Nelson
Heather A
HA
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000494:pharmacology*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D013028:Space Perception / Q000187:drug effects; D014626:Vaginal Smears
D019208:Brain-Derived Neurotrophic Factor; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D020932:Nerve Growth Factor