AGE-RELATED ALTERATIONS IN MITOCHONDRIAL PHYSIOLOGICAL PARAMETERS AND NITRIC OXIDE PRODUCTION IN SYNAPTIC AND NON-SYNAPTIC BRAIN CORTEX MITOCHONDRIA

AGE-RELATED ALTERATIONS IN MITOCHONDRIAL PHYSIOLOGICAL PARAMETERS AND NITRIC OXIDE PRODUCTION IN SYNAPTIC AND NON-SYNAPTIC BRAIN CORTEX MITOCHONDRIA
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DOI:
10.1016/j.neuroscience.2011.04.060
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发表时间:
2011-08-11
期刊:
影响因子:
3.3
通讯作者:
Bustamante, J.
Bustamante, J.
中科院分区:
医学3区
文献类型:
--
作者:
Lores-Arnaiz, S.;Bustamante, J.

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大脑老化与线粒体功能障碍和一氧化氮水平的变化有关。本研究的目的是评估突触和非突触线粒体对衰老依赖性功能障碍的敏感性。与3月龄小鼠相比,14月龄小鼠大脑皮层突触体的3态呼吸频率和呼吸控制率分别降低了43%和33%。呼吸频率不受非突触线粒体部分老化的显著影响。线粒体功能障碍与14月龄小鼠大脑皮质突触体和非突触线粒体H(2)O(2)生成率分别增加84%和38%有关。与非突触线粒体相比,14月龄小鼠的突触线粒体似乎更容易受到钙的伤害,这是通过两种类型的线粒体对钙诱导的去极化的反应来衡量的。随着年龄的增长,突触体组分和非突触组分的一氧化氮(NO)生成量分别减少44%和27%。这项研究的结果表明,随着年龄的增长,神经末梢的线粒体功能更容易受到突触活动导致的持续钙变化的影响。非突触线粒体将对年龄相关的功能障碍和氧化损伤更具抵抗力。(C)2011年IBRO。爱思唯尔有限公司出版。保留所有权利。
Brain aging has been associated with mitochondrial dysfunction and changes in nitric oxide levels. The aim of this study was to evaluate the susceptibility of synaptic and non-synaptic mitochondria to aging-dependent dysfunction. State 3 respiratory rate and respiratory control were 43% and 33% decreased, respectively in brain cortex synaptosomes from 14-month-old animals, as compared with synaptosomes from 3-month-old mice. Respiratory rates were not significantly affected by aging in non-synaptic mitochondrial fractions. Mitochondrial dysfunction was associated with increases of 84% and 38% in H(2)O(2) production rates in brain cortex synaptosomes and non-synaptic mitochondria, respectively, from 14-month-old mice, as compared with young animals. Synaptic mitochondria seem to be more susceptible to calcium insult in 14-month-old mice, as compared with non-synaptic mitochondria, as measured by response of both types of fractions to calcium-induced depolarization. With aging, nitric oxide (NO) production was 44% and 27% decreased both in synaptosomal and non-synaptic mitochondrial fractions, respectively. The results of this study suggest that with aging, mitochondrial function at the nerve terminals would be more susceptible to suffer alterations by the constant calcium changes occurring as a consequence of synaptic activity. Non-synaptic mitochondria would be more resistant to age-related dysfunction and oxidative damage. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.