The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson's disease
The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson's disease
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DOI：
10.1016/j.lfs.2011.03.010
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发表时间：
2011-05-09
期刊：
影响因子：
6.1
通讯作者：
Kamal, Hanan
中科院分区：
文献类型：
--
作者：
Baraka, Azza M.;Korish, Aida A.;Kamal, Hanan
目的：本研究的目的是评估和比较17 β-雌二醇和两种不同的选择性雌激素受体调节剂（SERM），他莫昔芬和雷洛昔芬，以及选择性雌激素受体α激动剂，丙基吡唑三醇（PPT）和选择性雌激素受体β激动剂，二芳基丙腈（DPN），对6-羟多巴胺（6-OHDA）诱导的大鼠黑质多巴胺能细胞死亡的行为学和生化改变的影响。将动物分成8个相等的组：第I组;假手术组，第II组;经受卵巢切除术（OVX）组，第III组; OVX大鼠接受6-OHDA的纹状体注射，第IV-VIII组; OVX大鼠接受6-OHDA的纹状体注射，并且在6-OHDA之前每天分别注射17 β-雌二醇、他莫昔芬、雷洛昔芬、PPT和DPN，持续5天，并且继续另外2周。结果表明，纹状体注射6-OHDA可产生明显的行为学改变，提示PD。同时纹状体多巴胺、高香草酸（HVA）和3，4-二羟基苯乙酸（DOPAC）浓度显著降低。6-OHDA诱导的黑质多巴胺能细胞死亡的特征在于氧化应激，证明了纹状体谷胱甘肽过氧化物酶活性的显着降低，以及细胞凋亡，证明了黑质caspase-3活性的显着增加。治疗与17 β-雌二醇，雷洛昔芬，PPT，但既不是他莫昔芬也DPN，导致在显着改善的行为和生化变化诱导的6-OHDA.Significance：这些研究结果表明，雌激素和一些SERM具有雌激素激动剂活性的大脑，如雷洛昔芬，可能会发挥有益的效果在PD。(C)2011 Elsevier Inc. All rights reserved.
Aim: The aim of the present study was to assess and compare the effect of 17 beta-estradiol and two different selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene, as well as a selective estrogen receptor alpha agonist, propyl-pyrazole-triol (PPT) and a selective estrogen receptor beta agonist, diarylpropionitrile (DPN), on behavioral and biochemical alterations in 6-hydroxydopamine (6-OHDA)-induced nigral dopaminergic cell death in rats.Main methods: 80 female Wister rats were used. Animals were divided into eight equal groups: Group I; Sham operated, Group II; subjected to ovariectomy (OVX), Group III; OVX rats received striatal injection of 6-OHDA, Groups IV-VIII; OVX rats received striatal injection of 6-OHDA and were injected daily with 17 beta-estradiol, tamoxifen, raloxifene, PPT and DPN respectively for 5 days before 6-OHDA and continued for further 2 weeks.Key findings: Results showed that striatal injection of 6-OHDA produced significant behavioral alteration suggestive of PD. together with significant decrease in striatal dopamine, homovanillic acid (HVA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) concentrations. 6-OHDA-induced nigral dopaminergic cell death was characterized by oxidative stress, evidenced by significant decrease in striatal glutathione peroxidase activity, as well as apoptosis, evidenced by significant increase in nigral caspase-3 activity. Treatment with 17 beta-estradiol, raloxifene, PPT, but neither tamoxifen nor DPN, resulted in significant amelioration of the behavioral and biochemical alterations induced by 6-OHDA.Significance: These findings suggest that estrogen and some SERMs having estrogenic agonist activity in the brain, like raloxifene, might exert beneficial effect in PD. (C) 2011 Elsevier Inc. All rights reserved.