Effects of (-)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice.
Effects of (-)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice.
复制标题
（ - ） - 上chin对老年小鼠海马中TAU神经炎症和过度磷酸化的影响。
DOI：
10.1039/d0fo02438d
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发表时间：
2020-12-01
期刊：
影响因子：
6.1
通讯作者：
Ramirez-Sanchez I
中科院分区：
文献类型：
--
作者：
Navarrete-Yañez V ;Garate-Carrillo A ;Rodriguez A ;Mendoza-Lorenzo P ;Ceballos G ;Calzada-Mendoza C ;Hogan MC ;Villarreal F ;Ramirez-Sanchez I
有证据表明氧化应激（OS）和炎症是神经退行性病变的驱动因素。我们先前报道了（-）-表儿茶素（Epi）治疗对衰老诱导的OS及其恢复26个月大雄性小鼠前额叶皮层线粒体生物合成调节剂的能力的有益作用。在本研究中，使用相同的小鼠衰老模型，我们检查了Epi减轻海马OS、炎症、tau蛋白过度磷酸化、可溶性β-淀粉样蛋白水平、细胞存活、记忆、焦虑样行为水平以及全身炎症的能力。小鼠接受4周Epi治疗（1 mg/kg/天），并获得海马样品。对OS标志物蛋白质羰基和丙二醛水平的评估表明，随着年龄的增长，这些指标显著增加（约3倍），并被Epi部分抑制。胶质细胞酸性蛋白、炎症因子1（Iba 1）、促炎细胞因子、白细胞介素（IL-1β、IL-3、5、6和15）、环氧化酶2、肿瘤坏死因子α、核因子激活的B细胞和干扰素γ的蛋白水平随着年龄的增长而增加，并且在Epi治疗后也显著降低。然而，抗炎细胞因子，IL-1 ra，IL-10和IL-11在衰老过程中下降，并与Epi恢复。Epi还逆转了对tau过度磷酸化的衰老效应，增加了可溶性β-淀粉样蛋白水平（约2倍），细胞死亡（根据半胱天冬酶3和9活性），以及神经生长因子和触发受体髓样细胞2水平的降低。焦虑的措施，如行为和记忆表现出改善与肾上腺素治疗。全身炎症指标随着年龄的增长而升高，Epi能够降低血液炎症标志物。总之，结果证明Epi减轻海马OS和炎症的显著能力，从而改善脑功能。
Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (−)-epicatechin (Epi) treatment, on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble β-amyloid protein levels, cell survival, memory, anxiety-like behavior levels as well as systemic inflammation. Mice underwent 4 weeks of Epi treatment (1 mg/kg/day) and samples of hippocampus were obtained. Assessments of the OS markers protein carbonyls and malondialdehyde levels demonstrated significant increases (~3 fold) with aging that were partially suppressed by Epi. Protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), proinflammatory cytokines, interleukins (IL-1β, IL-3, 5, 6 and 15), ciclooxygenase 2, tumor necrosis factor α, nuclear factor activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, Il-10 and 11 were decreased in aging and were restored with Epi. Epi also reversed aging effects on the hyperphosporylation of tau, increased soluble β-amyloid levels (~2 fold), cell death, (as per caspase 3 and 9 activity), and reductions in nerve growth factor and triggering receptor myeloid cells 2 levels. Measures of anxiety like behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation were elevated with aging and Epi was capable to decrease blood inflammatory markers. Altogether, results evidence a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function.
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