Impact of estrogen receptor agonists and model of menopause on enzymes involved in brain metabolism, acetyl-CoA production and cholinergic function.
Impact of estrogen receptor agonists and model of menopause on enzymes involved in brain metabolism, acetyl-CoA production and cholinergic function.
复制标题
雌激素受体激动剂和更年期模型对参与脑代谢、乙酰辅酶A产生和胆碱能功能的酶的影响。
DOI：
10.1016/j.lfs.2020.117975
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Gibbs,RB
中科院分区：
文献类型：
--
作者：
Kirshner,ZZ;Yao,JeffreyK;Li,Junyi;Long,Tao;Nelson,Doug;Gibbs,RB
我们的目标是了解循环雌激素的损失和雌激素替代如何影响大脑的生理和功能，特别是在涉及认知过程的大脑区域。我们最近进行了一项大型代谢组学研究，描述了绝经和雌激素受体（ER）激动剂治疗对海马、额叶皮质和纹状体神经化学靶点的影响。在这里，我们描述了对参与葡萄糖利用和能量产生的几种关键酶水平的影响，特别是磷酸果糖激酶、3-磷酸甘油醛脱氢酶和丙酮酸脱氢酶。我们还评估了对β-肌动蛋白和α-微管蛋白水平、胆碱乙酰转移酶（ChAT）活性和ATP柠檬酸裂合酶水平的影响。所有实验均在年轻成年大鼠中进行。实验1比较了卵巢切除术（OVX），手术绝经的模型，和4-乙烯基环己烯二环氧化物（VCD）-治疗，过渡性绝经的模型，在动情前期和动情间期收集的组织的影响。实验2使用一个单独的大鼠队列，以评估相同的目标在OVX和VCD治疗的大鼠雌二醇或选择性ER激动剂治疗。检测了循环动物与手术和过渡性绝经模型之间代谢酶表达的差异。这些差异具有模型依赖性、区域依赖性和时间依赖性，并受选择性ER激动剂的调节.总的来说，研究结果表明，卵巢功能丧失和ER激动剂治疗对OVX和VCD治疗的大鼠有不同的影响。这些差异可能有助于解释雌激素治疗对经历过手术与过渡性绝经的女性脑功能和认知的影响差异。
Our goal is to understand how loss of circulating estrogens and estrogen replacement affect brain physiology and function, particularly in brain regions involved in cognitive processes. We recently conducted a large metabolomics study characterizing the effects of rodent models of menopause and treatment with estrogen receptor (ER) agonists on neurochemical targets in hippocampus, frontal cortex, and striatum. Here we characterize effects on levels of several key enzymes involved in glucose utilization and energy production, specifically phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase, and pyruvate dehydrogenase. We also evaluated effects on levels of β-actin and α-tubulin, choline acetyltransferase (ChAT) activity, and levels of ATP citrate lyase. All experiments were conducted in young adult rats. Experiment 1 compared the effects of ovariectomy (OVX), a model of surgical menopause, and 4-vinylcyclohexene diepoxide (VCD)-treatments, a model of transitional menopause, with tissues collected at proestrus and at diestrus. Experiment 2 used a separate cohort of rats to evaluate the same targets in OVX and VCD-treated rats treated with estradiol or with selective ER agonists. Differences in the expression of metabolic enzymes between cycling animals and models of surgical and transitional menopause were detected. These differences were model-, region- and time- dependent, and were modulated by selective ER agonists. Collectively, the findings demonstrate that loss of ovarian function and ER agonist treatments have differing effects in OVX vs. VCD-treated rats. Differences may help to explain differences in the effects of estrogen treatments on brain function and cognition in women who have experienced surgical vs. transitional menopause.