Carrascal Livia, Gorton Ella, Pardillo-Díaz Ricardo, Perez-García Patricia, Gómez-Oliva Ricardo, Castro Carmen, Nunez-Abades Pedro
Departament of Physiology, Pharmacy School, University of Seville, 41012 Seville, Spain.
Biomedical Research and Innovation Institute of Cadiz (INIBICA), 11003 Cadiz, Spain.
Antioxidants (Basel). 2020 Dec 19;9(12):1307. doi: 10.3390/antiox9121307.
Oxidative stress is one of the main proposed mechanisms involved in neuronal degeneration. To evaluate the consequences of oxidative stress on motor cortex pyramidal neurons during postnatal development, rats were classified into three groups: Newborn (P2-P7); infantile (P11-P15); and young adult (P20-P40). Oxidative stress was induced by 10 µM of cumene hydroperoxide (CH) application. In newborn rats, using the whole cell patch-clamp technique in brain slices, no significant modifications in membrane excitability were found. In infantile rats, the input resistance increased and rheobase decreased due to the blockage of GABAergic tonic conductance. Lipid peroxidation induced by CH resulted in a noticeable increase in protein-bound 4-hidroxynonenal in homogenates in only infantile and young adult rat slices. Interestingly, homogenates of newborn rat brain slices showed the highest capacity to respond to oxidative stress by dramatically increasing their glutathione and free thiol content. This increase correlated with a time-dependent increase in the glutathione reductase activity, suggesting a greater buffering capacity of newborn rats to resist oxidative stress. Furthermore, pre-treatment of the slices with glutathione monoethyl ester acted as a neuroprotector in pyramidal neurons of infantile rats. We conclude that during maturation, the vulnerability to oxidative stress in rat motor neurons increases with age.
氧化应激是神经元变性的主要潜在机制之一。为了评估出生后发育过程中氧化应激对运动皮层锥体神经元的影响，将大鼠分为三组：新生大鼠（P2 - P7）；幼鼠（P11 - P15）；和年轻成年大鼠（P20 - P40）。通过应用10 µM氢过氧化异丙苯（CH）诱导氧化应激。在新生大鼠中，使用脑片的全细胞膜片钳技术，未发现膜兴奋性有明显改变。在幼鼠中，由于GABA能强直电导的阻断，输入电阻增加，基强度降低。CH诱导的脂质过氧化仅在幼鼠和年轻成年大鼠脑片的匀浆中导致蛋白质结合的4 - 羟基壬烯醛显著增加。有趣的是，新生大鼠脑片的匀浆通过显著增加其谷胱甘肽和游离巯基含量，表现出对氧化应激的最高反应能力。这种增加与谷胱甘肽还原酶活性的时间依赖性增加相关，表明新生大鼠具有更强的抵抗氧化应激的缓冲能力。此外，用谷胱甘肽单乙酯预处理脑片对幼鼠锥体神经元起到神经保护作用。我们得出结论，在成熟过程中，大鼠运动神经元对氧化应激的易感性随年龄增加。
