Age-dependent action of reactive oxygen species on transmitter release in mammalian neuromuscular junctions

作者：Shakirzyanova Anastasia^*; Valeeva Guzel; Giniatullin Arthur; Naumenko Nikolay; Fulle Stefania; Akulov Anton; Atalay Mustafa; Nikolsky Eugeny; Giniatullin Rashid

来源：Neurobiology of Aging, 2016, 38: 73-81.

DOI：10.1016/j.neurobiolaging.2015.10.023

• Acetylcholine release
• Neuromuscular
• Reactive oxygen species
• Newborn
• Aging

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 endplate 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.

• 出版日期2016-2