REVERSAL OF AGE-RELATED INCREASE IN BRAIN PROTEIN OXIDATION, DECREASE IN ENZYME-ACTIVITY, AND LOSS IN TEMPORAL AND SPATIAL MEMORY BY CHRONIC ADMINISTRATION OF THE SPIN-TRAPPING COMPOUND N-TERT-BUTYL-ALPHA-PHENYLNITRONE
REVERSAL OF AGE-RELATED INCREASE IN BRAIN PROTEIN OXIDATION, DECREASE IN ENZYME-ACTIVITY, AND LOSS IN TEMPORAL AND SPATIAL MEMORY BY CHRONIC ADMINISTRATION OF THE SPIN-TRAPPING COMPOUND N-TERT-BUTYL-ALPHA-PHENYLNITRONE
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DOI：
10.1073/pnas.88.9.3633
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发表时间：
1991-05-01
影响因子：
11.1
通讯作者：
FLOYD, RA
中科院分区：
文献类型：
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作者：
CARNEY, JM;STARKEREED, PE;FLOYD, RA
氧自由基和氧化事件已被认为在衰老期间发生的细胞功能变化中发挥作用。 大脑容易发生氧化损伤，因此确定衰老诱导的大脑变化是否与氧化事件有关是很重要的。 以前我们证明了缺血/再灌注损伤引起的脑损伤涉及氧化事件。 此外，预处理与自旋捕获化合物N-叔丁基-α-苯基硝酮（PBN）减少了氧化蛋白的增加和谷氨酰胺合成酶（GS）的活性的损失，伴随着缺血/再灌注损伤的脑。 我们在这里报告说，老年沙鼠有一个显着较高的水平的氧化蛋白质的羰基残基和GS和中性蛋白酶活性下降相比，年轻的成年沙鼠评估。 我们还发现，慢性处理与自旋捕获化合物PBN引起的氧化蛋白水平的下降和增加的GS和中性蛋白酶活性在老年蒙古沙鼠脑。 与老年沙鼠相比，PBN治疗年轻成年沙鼠对脑氧化蛋白含量或GS活性没有显着影响。 雄性沙鼠，年轻成年人（3个月大）和退休的饲养员（15-18个月大），用PBN治疗14天，每日两次剂量为32 mg/kg。 如果PBN给药2周后停止，氧化蛋白的水平显着降低，增加GS和中性蛋白酶活性在老年沙鼠改变单调的方式回到老年沙鼠PBN给药前观察到的水平。 我们还报告说，老年沙鼠作出更多的错误比年轻的动物和老年沙鼠治疗PBN作出更少的错误，在径向臂迷宫测试的时间和空间的记忆比未经处理的老年对照。 这些数据可以解释为表明细胞蛋白质的氧化可能是脑功能的关键决定因素。 此外，它还意味着，有一个与年龄相关的增加，在脆弱性的组织氧化，可以修改的自由基捕获化合物。
Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls. These data can be interpreted to indicate that oxidation of cellular proteins may be a critical determinant of brain function. Moreover, it also implies that there is an age-related increase in vulnerability of tissue to oxidation that can be modified by free radical trapping compounds.