Cardoso_2010_Eur.J.Pharmacol_634_192

The aim of the present study was to investigate the effects of 17beta-estradiol on expression of muscarinic acetylcholine receptor subtypes (M1 to M5) and estrogen receptor alpha, in the rat hippocampus. Hippocampi were obtained from rats in proestrus, rats ovariectomized for 15 days, rats ovariectomized for 15 days and then treated with 17beta-estradiol for 7 days, and rats ovariectomized and immediately treated with 17beta-estradiol for 21 days. Expression of M1 to M5 was increased in hippocampi of rats ovariectomized for 15 days compared to rats in proestrus. Although this effect was abolished when replacement with 17beta-estradiol started immediately after ovariectomy, the increased expression of M1, M3 and M5 receptor subtypes was unchanged when replacement with 17beta-estradiol started only 15 days after ovariectomy. The expression of estrogen receptor alpha in the hippocampus was also upregulated after ovariectomy when compared to rats in proestrus. This effect was abolished when 17beta-estradiol was replaced immediately after ovariectomy, and slightly reduced when the replacement started 15 days after ovariectomy. The replacement with estrogen also had beneficial effects on cognitive function, as suggested by data obtained in the plus-maze discriminative avoidance task. In conclusion, the present results provide evidence that 17beta-estradiol regulates the expression of muscarinic acetylcholine receptor subtypes and estrogen receptor alpha. The immediate replacement with estrogen seems critical to restore the expression of these receptors after hormonal deprivation. The understanding of the regulation of expression and intracellular signaling of the muscarinic acetylcholine receptor subtype M1 and the estrogen receptor alpha may be helpful to elucidate the mechanisms involved in changes of cognitive function in postmenopausal women and in neurodegenerative diseases.