Regional serotonin metabolism in the brain of transgenic mice lacking monoamine oxidase A.
The effect of a lack of the gene encoding monoamine oxidase A (MAO A) in transgenic Tg8 mice on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and on the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain, hypothalamus, hippocampus, striatum, amygdala, and frontal cortex was studied. It was shown that mice with a genetic MAO A knockout differed from mice of the initial C3H/HeJ strain in having a higher level of 5-HT and a lower level of its metabolite, 5-HIAA, in all brain regions but the frontal cortex, where the changes were insignificant. Although the 5-HIAA/5-HT ratio in various brain regions differed considerably, the decrease of the 5-HT oxidative deamination index in Tg8 mice was similar in different brain regions (to 41-45% of control values), with the exception of the frontal cortex, where the decrease of the 5-HIAA/5-HT was somewhat smaller (to 54%). The presence of the remaining 45% +/- 1.9% of the control ratio value indicates rather effective oxidative deamination of 5-HT in MAO A knockout mice and explains the lack of severe behavioral and pathological consequences in MAO A genetic deficiency. An increase of TPH activity in mice lacking MAO A was found in the frontal cortex, hippocampus, and amygdala. No significant changes were found in the striatum, hypothalamus, and midbrain. The data show an effect of the MAO A gene mutation on TPH and indicate a uniform decrease of 5-HT catabolism in different brain regions except for the frontal cortex, which is somewhat more resistant to the lack of MAO A than other brain structures.
Popova
N K
NK
Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia. npopova@bionet.nsc.ru
Gilinsky
M A
MA
Amstislavskaya
T G
TG
Morosova
E A
EA
Seif
I
I
De Maeyer
E
E
D000679:Amygdala / Q000201:enzymology; D000818:Animals; D001921:Brain / Q000201:enzymology*; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology; D006624:Hippocampus / Q000201:enzymology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000201:enzymology; D008297:Male; D008636:Mesencephalon / Q000201:enzymology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008995:Monoamine Oxidase / Q000172:deficiency*; D009154:Mutation / Q000502:physiology*; D017072:Neostriatum / Q000201:enzymology; D012701:Serotonin / Q000096:biosynthesis*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase