Dimethyl sulfoxide suppresses NMDA- and AMPA-induced ion currents and calcium influx and protects against excitotoxic death in hippocampal neurons.
Dimethyl sulfoxide (DMSO) is widely used in neuroscience research as a solvent for various pharmacological agents in both cell culture and in vivo studies and is also used in humans to treat musculoskeletal problems and pain. We now report that concentrations of DMSO to which neurons are typically exposed in experimental studies and in human patients (0.5-1.5%) inhibit glutamate responses in hippocampal neurons. DMSO suppresses, in a rapidly reversible manner, electrophysiological responses and calcium influx induced by glutamate, N-methyl-d-aspartate, and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate. Moreover, DMSO can prevent excitotoxic death of the neurons. These findings have important implications for the use of DMSO as a solvent in studies that involve glutamatergic neurotransmission. Our data also identify a mechanism that might explain clinical effects of DMSO on both peripheral and CNS neurons and suggest a potential use for DMSO in the treatment of excitotoxic neurodegenerative conditions.
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Laboratory of Neurosciences, Gerontology Research Center 4F01, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Mattson
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium; D016257:Fura-2; D004121:Dimethyl Sulfoxide