Shakirzyanova Anastasia, Valeeva Guzel, Giniatullin Arthur, Naumenko Nikolay, Fulle Stefania, Akulov Anton, Atalay Mustafa, Nikolsky Eugeny, Giniatullin Rashid
Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center, Russian Academy of Sciences, Kazan, Russia; Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia.
Neurobiol Aging. 2016 Feb;38:73-81. doi: 10.1016/j.neurobiolaging.2015.10.023. Epub 2015 Oct 31.
Reactive oxygen species (ROS) are implicated in aging, but the neurobiological mechanisms of ROS action are not fully understood. Using electrophysiological techniques and biochemical assays, we studied the age-dependent effect of hydrogen peroxide (H2O2) on acetylcholine release in rat diaphragm neuromuscular junctions. H2O2 significantly inhibited both spontaneous (measured as frequency of miniature end-plate potentials) and evoked (amplitude of end-plate potentials) transmitter release in adult rats. The inhibitory effect of H2O2 was much stronger in old rats, whereas in newborns tested during the first postnatal week, H2O2 did not affect spontaneous release from nerve endings and potentiated end-plate potentials. Proteinkinase C activation or intracellular Ca2+ elevation restored redox sensitivity of miniature end-plate potentials in newborns. The resistance of neonates to H2O2 inhibition was associated with higher catalase and glutathione peroxidase activities in skeletal muscle. In contrast, the activities of these enzymes were downregulated in old rats. Our data indicate that the vulnerability of transmitter release to oxidative damage strongly correlates with aging and might be used as an early indicator of senescence.
活性氧（ROS）与衰老有关，但其作用的神经生物学机制尚未完全明确。我们运用电生理技术和生化分析方法，研究了过氧化氢（H2O2）对大鼠膈神经肌肉接头处乙酰胆碱释放的年龄依赖性影响。H2O2显著抑制成年大鼠的自发递质释放（以微小终板电位频率衡量）和诱发递质释放（终板电位幅度）。H2O2对老年大鼠的抑制作用更强，而在出生后第一周内测试的新生大鼠中，H2O2不影响神经末梢的自发释放，反而增强了终板电位。蛋白激酶C激活或细胞内Ca2+升高可恢复新生大鼠微小终板电位的氧化还原敏感性。新生儿对H2O2抑制的抗性与骨骼肌中过氧化氢酶和谷胱甘肽过氧化物酶的较高活性有关。相反，老年大鼠中这些酶的活性下调。我们的数据表明，递质释放对氧化损伤的易感性与衰老密切相关，可能作为衰老的早期指标。
