A component of Premarin (R) enhances multiple cognitive nicotinic receptor expression

作者：Talboom Joshua S; Engler Chiurazzi Elizabeth B; Whiteaker Paul; Simard Alain R; Lukas Ronald; Acosta Jazmin I; Prokai Laszlo; Bimonte Nelson Heather A^*

来源：Hormones and Behavior, 2010, 58(5): 917-928.

DOI：10.1016/j.yhbeh.2010.09.002

• Premarin (R)
• Estrogen
• Delta(8,9)-dehydroestrone
• Equilin
• Learning
• Memory
• Nicotinic acetylcholine receptor
• Working memory
• Reference memory

In women, ovarian hormone loss at menopause has been related to cognitive decline, and some studies suggest that estrogen-containing hormone therapy (HT) can mitigate these effects. Recently, the Women's Health Initiative study found that conjugated equine estrogens, the most commonly prescribed HT, do not benefit cognition. Isolated components of conjugated equine estrogens (tradename Premarin (R)) have been evaluated in vitro, with delta(8,9)-dehydroestrone (Delta(8)E1) and equilin showing the strongest neuroprotective profiles. It has not been evaluated whether Delta(8)E1 or equilin impact cognition or the cholinergic system, which is affected by other estrogens and known to modulate cognition. Here, in middle-aged, ovariectomized rats, we evaluated the effects of Delta(8)E1 and equilin treatments on a cognitive battery and cholinergic nicotinic receptors (nAChR). Specifically, we used (125)I-labeled epibatidine binding to assay brain nicotinic receptor containing 4 alpha and 2 beta subunits (alpha 4 beta 2-nAChR), since this nicotinic receptor subtype has been shown previously to be sensitive to other estrogens. Delta(8)E1 enhanced spatial working, recent and reference memory. Delta(8)E1 also decreased hippocampal and entorhinal cortex alpha 4 beta 2-nAChR expression, which was related to spatial reference memory performance. Equilin treatment did not affect spatial memory or rat alpha 4 beta 2-nAChR expression, and neither estrogen impacted (86)Rb(+) efflux, indicating lack of direct action on human alpha 4 beta 2 nAChR function. Both estrogens influenced vaginal smear profiles, uterine weights, and serum luteinizing hormone levels, analogous to classic estrogens. The findings indicate that specific isolated Premarin (R) components differ in their ability to affect cognition and nAChR expression. Taken with the works of others showing Delta(8)E1-induced benefits on several dimensions of health-related concerns associated with menopause, this body of research identifies Delta(8)E1 as a new avenue to be investigated as a potential component of HT that may benefit brain health and function during aging.

• 出版日期2010-11