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.
Mössner
R
R
Department of Psychiatry and Psychotherapy, University of Würzburg, Federal Republic of Germany. rainald.moessner@mail.uni-wuerzburg.de
Dringen
R
R
Persico
A M
AM
Janetzky
B
B
Okladnova
O
O
Albert
D
D
Götz
M
M
Benninghoff
J
J
Schmitt
A
A
Gerlach
M
M
Riederer
P
P
Lesch
K P
KP
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