Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

Abstract

SummaryDeficits in learning and memory accompanied by agerelated neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in CA1 areas of hippocampal slices. Our results demonstrated that the impaired LTP induced by aging could be reversed by acute administration of reductants that can regulate thiol redox status directly, such as dithiothreitol or b-mercaptoethanol, but not by classical anti-oxidants such as vitamin C or trolox. This repair was mediated by the recruitment of aging-related deficits in NMDAR function induced by these reductants and was mimicked by glutathione, which can restore the age-associated alterations in endogenous thiol redox status. Moreover, antioxidant prevented but failed to reverse H 2 O 2 -induced impairment of NMDARmediated synaptic plasticity. These results indicate that the restoring of thiol redox status may be a more effective strategy than the scavenging of oxidants in the treatment of pre-existing oxidative injury in learning and memory.

Exploring the effect of vitamin C on sleep deprivation induced memory impairment

“…Treatment with VitC also restored learning and memory functions in rats exposed to fluoride (Raghu et al, 2013), and melamine (An and Zhang, 2014) via reducing the production of free-radicals from the hippocampus. Supplementation with VitC reduces or prevents memory impairment associated with diseases/conditions such as Alzheimer's disease (Harrison et al, 2009), and aging (Fotuhi et al, 2008;Kennard and Harrison, 2014;Yang et al, 2010). Finally, VitC was shown to prevent oxidative stress-induced damage in animal models of diabetes leading to improved cognitive functions (Bhutada et al, 2011;Hasanein and Shahidi, 2010).…”

“…It was shown to reduce learning and memory impairment associated with Alzheimer's diseases (Harrison et al, 2009), chronic stress (Heo et al, 2013;Kumar et al, 2009;Tagliari et al, 2011), diabetes (Bhutada et al, 2011;Hasanein and Shahidi, 2010), exposure to fluoride (Raghu et al, 2013), and melamine (An and Zhang, 2014), and the aging process (Fotuhi et al, 2008;Kennard and Harrison, 2014;Yang et al, 2010). In the current study, the possible preventive effect of VitC on impairment of memory induced by chronic sleep deprivation was examined.…”

New Insights onNOXEnzymes in the Central Nervous System

“…Numerous receptors of the CNS are regulated by redox modulation of cysteine residues, including NMDA (190), opioid (141), and gamma-aminobutyric acid receptors (26 There are arguments that the redox state might play a role during development. The shaping of the CNS is a result of a coordinated process involving not only cell proliferation and differentiation/migration but also cell death.…”

Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo

“…Hippocampal slices were prepared as previously described (Yang et al, 2010). In brief, anaesthetized mice was decapitated and transverse hippocampal slices were made with a Vibrate tissue slicer in ice-cold artificial cerebrospinal fluid.…”