title: Glutathione restores the mechanism of synaptic plasticity in aged mice to that of the adult.
abstract: 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.
authors.affiliation: Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Robillard
authors.forename: Grant R
authors.initials: GR
authors.lastname: Gordon
authors.forename: Hyun B
authors.initials: HB
authors.lastname: Choi
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
authors.forename: Brian A
authors.initials: BA
authors.lastname: MacVicar
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004594:Electrophysiology; D005978:Glutathione / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D016194:Receptors, N-Methyl-D-Aspartate; D005978:Glutathione; D000111:Acetylcysteine