Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 24, Issue 1, Pages 229-242Publisher
WILEY
DOI: 10.1111/j.1460-9568.2006.04867.x
Keywords
aging; estradiol; hippocampus; hormone replacement; reference memory
Categories
Funding
- NIA NIH HHS [R01 AG010755, R03 AG023925-01] Funding Source: Medline
- NIDA NIH HHS [P50 DA16511] Funding Source: Medline
Ask authors/readers for more resources
While some research has indicated that ovarian hormone therapy (HT) benefits memory and decreases risk of Alzheimer's disease in menopausal women, several newer studies have shown null or detrimental effects. Despite the null and negative cognitive findings, the numerous studies showing positive effects beg the question of what factors determine whether HT acts as a neuroprotectant or a risk factor for brain functioning. Using middle-aged female rats, we directly compared six HTs. We evaluated the effects of ovariectomy, tonic low-dose, tonic high-dose and biweekly cyclic estradiol treatment, as well as whether progesterone altered the effectiveness of any one of these oestrogen regimens. Animals were tested on spatial and complex cued (intramaze patterns) reference memory using variants of the Morris maze. The tonic low-dose and cyclic estradiol treatments improved spatial performance, while the addition of progesterone reversed these beneficial cognitive effects of estradiol. Additionally, all groups learned to locate the platform on the cued task; however, an egocentric circling strategy was used with sham ovary-intact and hormone-replacement groups showing the most efficient search strategy. Although the question of memory retention 8 weeks after the first cognitive assessment was addressed, a large number of animals died between the first and second test, rendering the retest uninterpretable for many group comparisons. Specifically, both doses of tonic estradiol dramatically increased the number of deaths during the 17-week experiment, while the cyclic estradiol treatment did not. Progesterone decreased the number of deaths due to tonic estradiol treatment. Our findings suggest that the dose of estradiol replacement as well as the presence of progesterone influences the cognitive outcome of estradiol treatment. Further, there appears to be a dissociation between HT effects on cognition and mortality rates.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available