Oxidative brain damage in aged mice. Protection by caloric reduction.
Oxidative brain damage in aged mice. Protection by caloric reduction.
复制标题
老年小鼠的氧化性脑损伤。
DOI：
10.1111/j.1749-6632.1995.tb16593.x
复制
发表时间：
1995
影响因子：
5.2
通讯作者：
Sohal,RS
中科院分区：
文献类型：
--
作者：
Lal,H;Forster,MJ;Sohal,RS
我们的实验是为了确定氧化性脑损伤是否介导了C57 BL/6 NNia小鼠脑功能的年龄相关性恶化。2老年小鼠感觉、运动和学习记忆能力下降。与自由采食组（AL）相比，维持低40%热量摄入（DR）的小鼠寿命延长43%，死亡率倍增时间延长31%。此外，在DR小鼠中，脑功能恶化的开始有显著延迟。9、17、23月龄AL组和DR组大鼠脑、心、肾组织中蛋白质羰基含量均显著增加，提示随着年龄的增长，氧化损伤程度也在增加。几乎所有的大脑区域都显示出蛋白质羰基含量的增加，老龄小鼠的纹状体和海马增加相对较大。除海马外，其他脑区膜蛋白巯基的丢失也随年龄增加而增加。热量限制显着延缓羰基蛋白的年龄相关的增加。这种减少在皮质中最为明显，而在海马体中仅适度减少。对神经保护机制的研究表明，AL组脑组织中线粒体状态4呼吸速率随年龄增加而增加，而DR组则无此现象。因此，在DR小鼠中的一个保护作用发生在氧自由基产生的部位。线粒体超氧化物和过氧化氢的产生率随着年龄的增长而增加，并且在每个年龄的所有三个器官中，AL小鼠的线粒体超氧化物和过氧化氢的产生率均高于DR小鼠。与此相反，没有明确的模式，年龄或饮食相关的变化提供的超氧化物歧化酶，过氧化氢酶，谷胱甘肽过氧化物酶的抗氧化防御。这些数据表明，增加的氧化应激损伤可能是脑老化和相关脑功能障碍的重要机制。这两种效果都可以通过热量优化来显著调节。
Our experiments were undertaken to determine if oxidative brain damage’me-diates age-associated deterioration reported in brain functions of C57BL/6NNia mice. 2 The aged mice exhibit deficits in sensory, motor and learning/rnemory capacity. Mice maintained on a caloric intake 40% less (DR) than an ad libitum fed group (AL) exhibited a 43% extension in life span and a 3 1% prolongation in mortality rate doubling time. Further, there was a significant retardation in the onset of the brain function deterioration in DR mice. There was a significant increase in the protein carbonyl content in brain, heart and kidney of AL and DR groups aged 9, 17, or 23 months suggesting an increase in the oxidative damage with age. Nearly all brain areas showed an increase in protein carbonyl content, with relatively larger increases in striatum and hippocampus of the aging mice. The loss of membrane protein sulfhydral groups also increased with age in all brain regions except hippocampus. The caloric restriction significantly retarded the age-associated increase in carbonyl protein. This reduction was most pronounced in cortex, whereas only a modest reduction was evident in the hippocampus. An investigation of the mechanisms underlying the neuroprotection showed that the mitochondrial state 4 respiratory rate in brain tissue was increased with age in the AL, but not the DR group. Thus, one protective effect in DR mice occurred at a site of oxygen free-radical generation. The rates of mitochondrial superoxide and hydrogen peroxide generation increased with age and were higher in the AL than DR mice in all the three organs at each age. In contrast, there was no clear-cut pattern of age-or diet-related changes in antioxidant defenses provided by superoxide dismutase, catalase, and glutathione peroxidase. These data suggest that increased oxidative stressldamage may be an important mechanism of brain aging and the associated brain dysfunctions. Both of these effects can be modulated significantly via caloric optimization.