Increased hippocampal DNA oxidation in serotonin transporter deficient mice.
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.
Department of Psychiatry and Psychotherapy, University of Würzburg, Federal Republic of Germany. rainald.moessner@mail.uni-wuerzburg.de
R
R
Mössner
R
R
Dringen
A M
AM
Persico
B
B
Janetzky
O
O
Okladnova
D
D
Albert
M
M
Götz
J
J
Benninghoff
A
A
Schmitt
M
M
Gerlach
P
P
Riederer
K P
KP
Lesch
D000818:Animals; D001921:Brain / Q000201:enzymology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009419:Nerve Tissue Proteins; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D014018:Tissue Distribution
D002352:Carrier Proteins; D018736:DNA Adducts; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D004247:DNA; D005979:Glutathione Peroxidase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse; D005978:Glutathione; D019803:Glutathione Disulfide