Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, Canada.
PLoS One. 2011;6(5):e20676. doi: 10.1371/journal.pone.0020676. Epub 2011 May 31.
Glutathione (GSH), the major endogenous antioxidant produced by cells, can modulate the activity of N-methyl-D-aspartate receptors (NMDARs) through its reducing functions. During aging, an increase in oxidative stress leads to decreased levels of GSH in the brain. Concurrently, aging is characterized by calcium dysregulation, thought to underlie impairments in hippocampal NMDAR-dependent long-term potentiation (LTP), a form of synaptic plasticity thought to represent a cellular model for memory. Here we show that orally supplementing aged mice with N-acetylcysteine, a precursor for the formation of glutathione, reverses the L-type calcium channel-dependent LTP seen in aged animals to NMDAR-dependent LTP. In addition, introducing glutathione in the intrapipette solution during whole-cell recordings restores LTP obtained in whole-cell conditions in the aged hippocampus. We conclude that aging leads to a reduced redox potential in hippocampal neurons, triggering impairments in LTP.
谷胱甘肽（GSH）是细胞产生的主要内源性抗氧化剂，可通过其还原功能调节 N-甲基-D-天冬氨酸受体（NMDAR）的活性。随着年龄的增长，氧化应激的增加会导致大脑中 GSH 水平降低。同时，衰老的特征是钙失调，据认为这是海马 NMDAR 依赖性长时程增强（LTP）受损的基础，LTP 是一种突触可塑性形式，被认为是记忆的细胞模型。在这里，我们表明，给老年小鼠口服补充 N-乙酰半胱氨酸（GSH 的前体）可将老年动物中观察到的 L 型钙通道依赖性 LTP 逆转回 NMDAR 依赖性 LTP。此外，在全细胞膜片钳记录中在细胞内液中引入谷胱甘肽可恢复在老年海马体中在全细胞膜条件下获得的 LTP。我们得出结论，衰老会导致海马神经元的还原电势降低，从而引发 LTP 受损。
