Abstract
The serotonin transporter (5HTT) is the molecule responsible for the high-affinity reuptake of 5HT from the synaptic cleft. Mice lacking the 5HTT exhibit highly elevated extracellular concentrations of 5HT. We assessed whether the glutathione detoxification system is altered in 5HTT-deficient mice. While levels of reduced and oxidized glutathione were unchanged, glutathione metabolising enzymes showed a differential pattern of modulation. Glutathione peroxidase was reduced in frontal cortex, brainstem, and cerebellum of 5HTT-deficient mice, though not to a statistically significant extent, while a putative isoform of the detoxifying enzyme glutathione-S-transferase pi was decreased in a number of brain regions, especially in brainstem. At the level of the DNA, we found an increase of oxidative DNA adducts in the hippocampus of 5HTT-deficient mice. Given the importance of the hippocampus in learning and memory, this may be the most important neurochemical consequence of the absence of the 5HTT.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / enzymology
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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DNA / metabolism*
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DNA Adducts / metabolism
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Glutathione / metabolism
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Glutathione Disulfide / metabolism
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Glutathione Peroxidase / metabolism
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Glutathione S-Transferase pi
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Glutathione Transferase / genetics
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Glutathione Transferase / metabolism
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Hippocampus / metabolism*
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Membrane Transport Proteins*
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Mice
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Mice, Knockout / genetics
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Nerve Tissue Proteins*
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Oxidation-Reduction
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Oxidative Stress / physiology
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RNA, Messenger / metabolism
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Serotonin Plasma Membrane Transport Proteins
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Tissue Distribution
Substances
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Carrier Proteins
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DNA Adducts
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Isoenzymes
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, mouse
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DNA
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Glutathione Peroxidase
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Glutathione S-Transferase pi
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Glutathione Transferase
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Gstp1 protein, mouse
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Glutathione
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Glutathione Disulfide