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雌激素对未经药物治疗的绝经后帕金森病患者黑质纹状体多巴胺能神经元的有益作用。

Beneficial effect of estrogen on nigrostriatal dopaminergic neurons in drug-naïve postmenopausal Parkinson's disease.

机构信息

Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.

出版信息

Sci Rep. 2019 Jul 19;9(1):10531. doi: 10.1038/s41598-019-47026-6.

Abstract

This study aimed to investigate the potential beneficial effects of estrogen on nigrostriatal dopaminergic neuron degeneration in postmenopausal drug-naïve Parkinson's disease (PD). Based on the ratio of lifetime estrogen exposure length to the total length of the estrogen exposure and deprivation period, postmenopausal women with drug-naïve PD were divided into low (n = 31) and high (n = 31) estrogen exposure ratio groups. We performed a comparative analysis of the striatal dopamine transporter (DAT) availability between the two groups. Additionally, we evaluated the longitudinal change in the levodopa equivalent dose per month using a linear mixed model. The motor symptoms were more severe in the low estrogen exposure ratio group than in the high estrogen exposure ratio group (P = 0.016). PD patients in the two groups had significantly lower DAT availability on all striatal sub-regions except for ventral striatum than did age- and sex-matched normal controls. When comparing the two groups, PD patients in the low estrogen exposure ratio group exhibited significantly lower DAT availability in the posterior putamen (P = 0.024) and in the ventral putamen (P = 0.036) than those in the high estrogen exposure ratio group. The estimated monthly levodopa equivalent dose changes were 10.9 in the low estrogen exposure ratio group and 7.1 in the high estrogen exposure ratio group with a significant interaction between the two groups (P = 0.001). These in vivo data provide indirect evidence showing that estrogen may elicit a beneficial effect on nigrostriatal dopamine neurons in PD.

摘要

本研究旨在探讨雌激素对绝经后初发帕金森病(PD)患者黑质纹状体多巴胺能神经元变性的潜在有益作用。基于雌激素暴露长度与雌激素暴露和剥夺期总长度的比值,将绝经后初发 PD 女性分为低(n=31)和高(n=31)雌激素暴露比组。我们对两组间纹状体多巴胺转运体(DAT)的可用性进行了比较分析。此外,我们使用线性混合模型评估了每月左旋多巴等效剂量的纵向变化。低雌激素暴露比组的运动症状比高雌激素暴露比组更严重(P=0.016)。两组 PD 患者除腹侧纹状体外,所有纹状体亚区的 DAT 可用性均明显低于年龄和性别匹配的正常对照组。两组比较时,低雌激素暴露比组 PD 患者的后壳核(P=0.024)和腹侧壳核(P=0.036)的 DAT 可用性明显低于高雌激素暴露比组。低雌激素暴露比组和高雌激素暴露比组的估计每月左旋多巴等效剂量变化分别为 10.9 和 7.1,两组间存在显著交互作用(P=0.001)。这些体内数据提供了间接证据,表明雌激素可能对 PD 中的黑质纹状体多巴胺神经元产生有益影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e633/6642214/7bd5452a3a15/41598_2019_47026_Fig1_HTML.jpg

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