Nathalie Arnal, Omar Castillo, María J T de Alaniz, Carlos A Marra
{"title":"Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration.","authors":"Nathalie Arnal, Omar Castillo, María J T de Alaniz, Carlos A Marra","doi":"10.1155/2013/645379","DOIUrl":null,"url":null,"abstract":"<p><p>Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A β (1-42)/(1-40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"645379"},"PeriodicalIF":0.0000,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836397/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Alzheimer's Disease","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2013/645379","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2013/11/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Neuroscience","Score":null,"Total":0}
引用次数: 0
Abstract
Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A β (1-42)/(1-40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements.
铜(Cu)和胆固醇(Cho)都与人类和动物模型中的神经退行性疾病有关。我们研究了在 Wistar 大鼠饮用水中口服微量铜(3 ppm)和/或胆固醇(2%)2 个月的效果。在血浆和大脑海马中观察到非脑磷脂结合的铜含量增加,同时血浆、大脑皮层和海马中脑磷脂浓度升高。Cu、Cho 和 Cu + Cho 组合处理能够诱导线粒体膜中的 Cho/磷脂比率升高,同时谷胱甘肽含量降低。心磷脂的浓度降低,过氧化产物(共轭二烯和脂过氧化物)的浓度升高。包括 Cho 在内的处理会导致线粒体外膜和内膜僵化,同时渗透性增加。除了用 Cu 和 Cho 处理的大鼠皮质外,没有观察到 Cyt C 向细胞膜渗漏的明显增加,Caspase-3 活性和 Bax/Bcl2 比率也没有明显变化。然而,皮质和海马的 A β (1-42)/(1-40) 比率较高。这些研究结果表明,Cu或Cho诱导的神经退行性病变过程刚刚开始,而这两种营养补充剂的结合可能会增强这一过程。