Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8
Curcumin prevents mitochondrial dysfunction in the brain of the senescence-accelerated mouse-prone 8
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DOI：
10.1016/j.neuint.2013.02.014
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发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Frank, Jan
中科院分区：
文献类型：
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作者：
Eckert, Gunter P.;Schiborr, Christina;Frank, Jan
衰老的大脑遭受线粒体功能障碍和ATP形式的能量可用性降低，这反过来可能导致或促进随着年龄的增长观察到的认知，感觉和运动功能的下降。需要显示人脑老化的一些病理特征的动物模型，以便研究通过例如饮食因素的预防。因此，我们研究了快速老化加速衰老小鼠倾向8（SAMP 8）菌株及其正常老化对照加速衰老小鼠抵抗1（SAMR 1）作为脑中线粒体功能年龄依赖性变化模型的适用性。为此，给2个月大的雄性SAMR 1（n = 10）和SAMP 8小鼠（n = 7）喂食西式饮食（对照组）5个月，给一组SAMP 8小鼠（n = 6）喂食用500 mg姜黄素/kg强化的相同饮食。分析分离的脑细胞和脑组织匀浆的丙二醛、血红素加氧酶-1 mRNA、线粒体膜电位（MMP）、ATP浓度、线粒体膜的线粒体标记蛋白（TIMM、TOMM）、线粒体渗透性转换孔（ANTI、VDAC 1、TSPO）、呼吸复合物以及分裂和融合（Fis、Opa 1、Mfn 1、Drp 1）的蛋白水平。从SAMP 8小鼠分离的分离的脑细胞显示MMP和ATP水平显著降低，这可能是由于复合物V蛋白表达显著减少和TSPO表达增加。分裂和融合标记蛋白表明SAMP 8小鼠脑中线粒体分裂增强。用姜黄素治疗SAMP 8小鼠改善MMP和ATP，并恢复线粒体融合，可能是通过上调核因子PGC 1 α蛋白表达。总之，与SAMR 1小鼠相比，SAMP 8是研究线粒体功能的年龄依赖性变化的合适模型，姜黄素成为预防伴随或由线粒体功能障碍引起的神经退行性疾病的有前途的营养药物。(C)2013爱思唯尔有限公司保留所有权利。
The aging brain suffers mitochondrial dysfunction and a reduced availability of energy in the form of ATP, which in turn may cause or promote the decline in cognitive, sensory, and motor function observed with advancing age. There is a need for animal models that display some of the pathological features of human brain aging in order to study their prevention by e.g. dietary factors. We thus investigated the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) as a model for the age-dependent changes in mitochondrial function in the brain. To this end, 2-months old male SAMR1 (n = 10) and SAMP8 mice (n = 7) were fed a Western type diet (control groups) for 5 months and one group of SAMP8 mice (n = 6) was fed an identical diet fortified with 500 mg curcumin per kg. Dissociated brain cells and brain tissue homogenates were analyzed for malondialdehyde, heme oxygenase-1 mRNA, mitochondrial membrane potential (MMP), ATP concentrations, protein levels of mitochondrial marker proteins for mitochondrial membranes (TIMM, TOMM), the mitochondrial permeability transition pore (ANTI, VDAC1, TSPO), respiration complexes, and fission and fusion (Fis, Opa1, Mfn1, Drp1). Dissociated brain cells isolated from SAMP8 mice showed significantly reduced MMP and ATP levels, probably due to significantly diminished complex V protein expression, and increased expression of TSPO. Fission and fusion marker proteins indicate enhanced mitochondrial fission in brains of SAMP8 mice. Treatment of SAMP8 mice with curcumin improved MMP and ATP and restored mitochondrial fusion, probably by up-regulating nuclear factor PGC1 alpha protein expression. In conclusion, SAMP8 compared to SAMR1 mice are a suitable model to study age-dependent changes in mitochondrial function and curcumin emerges as a promising nutraceutical for the prevention of neurodegenerative diseases that are accompanied or caused by mitochondrial dysfunction. (C) 2013 Elsevier Ltd. All rights reserved.