肠道多巴胺受体 D2在帕金森病小鼠模型中的神经保护作用的数据集

鉴于肠道DRD2是维持肠道中产生琥珀酸盐的Alleoprevotella以及调节大脑线粒体功能所必需的，我们推测来自Alleoprevotella的琥珀酸盐可能影响大脑中的线粒体，为肠道提供DRD2依赖性的神经保护。为了测试我们的推测，我们首先检查了琥珀酸对暴露于MPP+（神经毒素 MPTP 的活性代谢物）的 SH-SY5Y 人神经母细胞瘤细胞存活的影响（图 4.6 a）。使用CCK8活性试剂盒检测，我们发现用10 mM和20 mM琥珀酸盐预处理SH-SY5Y细胞可以显著抑制MPP+诱导的细胞死亡（图4.6 b）。在生物体中，已知琥珀酸通过电子传递链复合体II中的琥珀酸脱氢酶被转化为延胡索酸，该复合体参与线粒体中ATP 的产生 (Tretter, Patocs et al. 2016)。众所周知，MPP+可以抑制电子传递链复合物I (Cunha, Pazini et al. 2017)。因此，我们考察了琥珀酸盐的预处理是否有助于稳定神经保护的线粒体功能。正如预期的那样，通过测量线粒体膜电位（MMP），我们发现用不同剂量琥珀酸盐预处理 SH-SY5Y细胞显著保护线粒体免受MPP+诱导的损伤

Given that intestinal DRD2 is essential for maintaining succinate-producing *Alleoprevotella* in the gut and regulating cerebral mitochondrial function, we hypothesized that succinate from *Alleoprevotella* might affect mitochondria in the brain to provide DRD2-dependent neuroprotection for the gut. To test this hypothesis, we first examined the effect of succinate on the viability of SH-SY5Y human neuroblastoma cells exposed to MPP+, the active metabolite of the neurotoxin MPTP (Fig. 4.6a). Using the CCK8 activity assay kit, we found that pretreatment of SH-SY5Y cells with 10 mM and 20 mM succinate significantly inhibited MPP+-induced cell death (Fig. 4.6b). In vivo, succinate is known to be converted to fumarate via succinate dehydrogenase in complex II of the electron transport chain, which is involved in ATP production in mitochondria (Tretter, Patocs et al. 2016). It is well-established that MPP+ inhibits complex I of the electron transport chain (Cunha, Pazini et al. 2017). Therefore, we investigated whether succinate pretreatment could help stabilize mitochondrial function for neuroprotection. As expected, by measuring mitochondrial membrane potential (MMP), we found that pretreatment of SH-SY5Y cells with various doses of succinate significantly protected mitochondria against MPP+-induced damage.

搜集汇总

背景与挑战

背景概述

该数据集基于一项研究，探索肠道多巴胺D2受体（DRD2）在小鼠帕金森病模型中的神经保护作用，通过MPTP诱导多巴胺能神经变性实验，发现肠道DRD2信号和微生物组产生的琥珀酸对维持黑质多巴胺神经元存活至关重要。数据集包含实验数据，支持肠道-大脑轴在帕金森病机制中的角色，并提供潜在的神经炎症相关疾病干预策略。