Glutathione Restores the Mechanism of Synaptic Plasticity in Aged Mice to That of the Adult

被引：73

作者：

Robillard, Julie M. ^{[1
]}

Gordon, Grant R. ^{[1
]}

Choi, Hyun B. ^{[1
]}

Christie, Brian R. ^{[2
]}

MacVicar, Brian A. ^{[1
]}

机构：

[1] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC, Canada

[2] Univ Victoria, Isl Med Program, Victoria, BC, Canada

来源：

PLOS ONE | 2011年 / 6卷 / 05期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

LONG-TERM POTENTIATION; HIPPOCAMPAL AREA CA1; NMDA-RECEPTOR; PEROXIDE MODULATION; ASSOCIATIVE MEMORY; REDOX MODULATION; N-ACETYLCYSTEINE; CALCIUM STORES; CA2+ RELEASE; NEURONS;

D O I：

10.1371/journal.pone.0020676

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

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