Effects of 17β-estradiol on expression of muscarinic acetylcholine receptor subtypes and estrogen receptor α in rat hippocampus

被引：36
作者：
Cardoso, Camila Castellan [1 ]
Ricardo, Victor Proenca
Frussa-Filho, Roberto
Porto, Catarina Segreti [2 ]
Francis Abdalla, Fernando Mauricio [1 ]
机构：
[1] Inst Butantan, Pharmacol Lab, BR-05503900 Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Pharmacol, Sect Expt Endocrinol, Sao Paulo, Brazil
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2010年 / 634卷 / 1-3期
基金：
巴西圣保罗研究基金会;
关键词：
Muscarinic acetylcholine receptors subtype; Estrogen receptor alpha; 17; beta-estradiol; Ovariectomy; Hippocampus; DISCRIMINATIVE AVOIDANCE TASK; ACTIVATED PROTEIN-KINASE; DENDRITIC SPINE DENSITY; CENTRAL-NERVOUS-SYSTEM; BASAL FOREBRAIN; MESSENGER-RNA; CHOLINERGIC NEURONS; ALZHEIMERS-DISEASE; ULTRASTRUCTURAL-LOCALIZATION; SYNAPTIC PLASTICITY;
D O I：
10.1016/j.ejphar.2010.02.032
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The aim of the present study was to investigate the effects of 17 beta-estradiol on expression of muscarinic acetylcholine receptor subtypes (M-1 to M-5) 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 17 beta-estradiol for 7 days, and rats ovariectomized and immediately treated with 17 beta-estradiol for 21 days. Expression of M-1 to M-5 was increased in hippocampi of rats ovariectomized for 15 days compared to rats in proestrus. Although this effect was abolished when replacement with 17 beta-estradiol started immediately after ovariectomy, the increased expression of M-1, M-3 and M-5 receptor subtypes was unchanged when replacement with 17 beta-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 17 beta-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 17 beta-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 M-1 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. (C) 2010 Elsevier B.V. All rights reserved.
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收藏
页码：192 / 200
页数：9
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