Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.
Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus.
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大鼠脑海马中的性低氧缺氧失衡线粒体动力学。
DOI：
10.1155/2015/742059
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发表时间：
2015
影响因子：
1.5
通讯作者：
Kohli E
中科院分区：
文献类型：
--
作者：
Jain K;Prasad D;Singh SB;Kohli E
脑在低压缺氧时主要易受氧化应激和线粒体功能障碍的影响，从而因能量危机而发生神经退行性变。有证据表明，线粒体融合/分裂失衡和线粒体功能障碍之间存在高度关联。线粒体融合/分裂是近年来报道的一种发生在细胞线粒体网络中的动力学机制。因此，该研究调查了慢性暴露于低压缺氧（HH）期间异常线粒体动力学（融合/分裂）的时间变化和参与沿着线粒体功能紊乱。将Sprague-Dawley大鼠暴露于相当于25000英尺的模拟高海拔3、7、14、21和28天。测定线粒体形态、神经元内的分布、呼吸复合物的酶活性、Δ Δ Km、ADP：ATP和分裂/融合关键蛋白的表达。结果表明，与未暴露的大鼠脑海马相比，HH通过在神经元中观察到的受损的小线粒体诱导线粒体形态改变，线粒体功能紊乱，神经元过程中线粒体密度降低，表现为过度的线粒体碎片化（分裂）和线粒体融合减少。研究表明，线粒体动力学的不平衡是HH损伤期间海马神经元中发生的值得注意的机制之一。
Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission) along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH). The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψ m, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission) and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.