Journal
NEUROBIOLOGY OF AGING
Volume 35, Issue 5, Pages 1074-1085Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.11.007
Keywords
Aging; Oxidative stress; Lipid peroxidation; Neuronal excitability; Electrophysiology; Glutathione imaging; Lymnaea stagnalis; Redox balance; Identified neuron; gamma-Glutamylcysteine synthetase inhibition; Mollusk; Pyroglutamate
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Funding
- National Science and Engineering Research Council (NSERC) Canada
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Oxidative stress is frequently implicated in diminished electrical excitability of aging neurons yet the foundations of this phenomenon are poorly understood. This study explored links between alterations in cellular thiol-redox state and age-associated decline in electrical excitability in identified neurons (right pedal dorsal 1 [RPeD1]) of the gastropod Lymnaea stagnalis. Intracellular thiol redox state was modulated with either dithiothreitol or membrane permeable ethyl ester of the antioxidant glutathione (et-GSH). Neuronal antioxidant demand was manipulated through induction of lipid peroxidation with 2,2'-azobis-2- methyl-propanimidamide-dihydrochloride (AAPH). Glutathione synthesis was manipulated with buthionine sulfoximine (BSO). We show that; glutathione content of snail brains declines with age, whereas pyroglutamate content increases; treatment with AAPH and BSO alone aggravated the natural low excitability state of old RPeD1, but only the combination of AAPH + BSO affected electrical excitability of young RPeD1; et-GSH reversed this effect in young RPeD1; et-GSH and dithiothreitol treatment reversed age-associated low excitability of old RPeD1. Together, these data argue for a tight association between glutathione availability and the regulation of neuronal electrical excitability and indicate perturbation of cellular thiol-redox metabolism as a key factor in neuronal functional decline in this gastropod model of biological aging. (C) 2014 Elsevier Inc. All rights reserved.
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