Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis
Synaptic and mitochondrial physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis
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DOI：
10.1016/j.mad.2006.01.019
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发表时间：
2006-06-01
影响因子：
5.3
通讯作者：
Fattoretti, Patrizia
中科院分区：
文献类型：
--
作者：
Bertoni-Freddari, Carlo;Mocchegiani, Eugenio;Fattoretti, Patrizia
大脑的功能，例如学习和记忆，在衰老过程中衰退。作为中枢神经系统这些关键功能的结构相关物，突触连接的恶化可能在这种损害中起核心作用。目前对突触年龄相关变化的研究表明，接触的数字损失似乎会引发老年CNS的代偿反应，即老年个体中存活的连接区大于成年受试者。突触数量和大小的平衡变化的最终结果是，每立方微米神经元的总突触连接面积也在老化中减少，这可能是年龄相关的CNS性能的功能衰退的原因。在衰老过程中突触退化的决定因素中，相当多的近期研究支持线粒体代谢能力进行性下降的早期和关键作用，即选择细胞器池提供足够量的三磷酸腺苷的能力。定量超微结构研究以及呼吸链关键酶（细胞色素氧化酶和琥珀酸脱氢酶）的细胞化学研究表明，线粒体功能障碍在与衰老和神经退行性疾病相关的突触退化事件中发挥早期和核心作用。在各种原因中，参与锌离子稳态的多种机制和分子被认为在衰老的大脑中效率较低。因此，胞质溶胶中游离锌离子浓度（[Zn 2 +]（i））的短暂失衡可被认为是轻微线粒体损伤和突触病理学的不利触发因素。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Brain performances, e.g. learning and memory, decay during aging. Deterioration of synaptic junctions, as structural correlates of these key functions of the central nervous system, may play a central role in this impairment. Current research on the age-related changes of synapses is documenting that the numeric loss of contacts appears to trigger a compensatory reaction by the old CNS, i.e. the surviving junctional areas in old individuals are larger than in adult subjects. The final outcome of the balanced changes in synaptic number and size is that the overall synaptic junctional area per cubic micron of neuropil is also reduced in aging and this may account for the age-associated functional decay of CNS performances. Among the suggested determinants of synaptic deterioration in aging, a considerable number of recent studies support an early and pivotal role of the progressive decline of the mitochondrial metabolic competence, i.e. the capacity of select pools of organelles to provide adequate amounts of adenosine triphosphate. Quantitative ultrastructural studies together with cytochemistry of key enzymes of the respiratory chain (cytochrome oxidase and succinic dehydrogenase) have shown that mitochondrial dysfunctions play an early and central role in synaptic deterioration events associated with aging and neurodegenerative diseases. Among the various causes, the multiple mechanisms and molecules involved in zinc ion homeostasis have been supposed to be less efficient in the aging brain. Thus, a transient imbalance of free zinc ion concentration in the cytosol ([Zn2+](i)) can be considered an unfavourable trigger of subtle mitochondrial damage and synaptic pathology. (c) 2006 Elsevier Ireland Ltd. All rights reserved.