期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 7, 页码 2701-2706出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1817885116
关键词
glutathione; glutamate; neurotransmission; mEPSC; acivicin
资金
- National Institutes of Health, National Institute of Neurological Disorders and Stroke [K08NS057824]
- Johns Hopkins Brain Science Institute
- National Association for Research on Schizophrenia and Depression Young Investigator Award
- National Institute of Mental Health [MH-092443]
- National Institutes of Health Silvio O. Conte Center Grant [MH-094268]
- NIH [MH-084018, MH-105660, MH-107730]
- US Public Health Service [MH18501]
- Stanley Foundation
- S/R
Glutamate is the most abundant excitatory neurotransmitter, present at the bulk of cortical synapses, and participating in many physiologic and pathologic processes ranging from learning and memory to stroke. The tripeptide, glutathione, is one-third glutamate and present at up to low millimolar intracellular concentrations in brain, mediating antioxidant defenses and drug detoxification. Because of the substantial amounts of brain glutathione and its rapid turnover under homeostatic control, we hypothesized that glutathione is a relevant reservoir of glutamate and could influence synaptic excitability. We find that drugs that inhibit generation of glutamate by the glutathione cycle elicit decreases in cytosolic glutamate and decreased miniature excitatory postsynaptic potential (mEPSC) frequency. In contrast, pharmacologically decreasing the biosynthesis of glutathione leads to increases in cytosolic glutamate and enhanced mEPSC frequency. The glutathione cycle can compensate for decreased excitatory neurotransmission when the glutamate-glutamine shuttle is inhibited. Glutathione may be a physiologic reservoir of glutamate neurotransmitter.
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