Effect of thiamine deficiency on brain serotonin turnover.
Serotonin turnover has been investigated in regional brain areas of rats made thiamine deficient by pyrithiamine (PT). Following intracisternal injection of [14C]5-hydroxytryptamine ([14C]5-HT), a marked increase in the accumulation of [14C]5-hydroxyindoleacetic acid ([14C]5-HIAA) was found in the medulla-pons, hypothalamus and cerebral cortex. [14C]5-HT levels were normal in all of the brain areas except the cerebral cortex which had an increase of 58%. The ratio of [14C]5-HIAA/[14C]5-HT was significantly increased in every brain region of PT-treated rats except the cerebral cortex. Part of this increase in [14C]5-HIAA was shown to be due to impairment of active transport of this 5-HT metabolite out of the brain. However, increased 5-HT synthesis in the cerebellum, hypothalamus, striatum, hippocampus and cerebral cortex was demonstrated by measurement of 5-HT accumulation after inhibition of brain monoamine oxidase. PT-induced increase in endogenous 5-HIAA in the medulla-pons occurred simultaneously with the onset of neurological signs and both parameters were reversible by thiamine administration. These results suggest that acute thiamine deficiency, induced by PT, both increases brain 5-HT synthesis and impairs 5-HIAA efflux from the brain. There is a close correlation between neurological manifestations and changes in brain 5-HT metabolism in acute thiamine deficiency.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D011745:Pyrithiamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000378:metabolism*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D011745:Pyrithiamine