IN-VIVO STUDY OF THE KINETICS OF THIAMINE AND ITS PHOSPHOESTERS IN THE DEAFFERENTED RAT CEREBELLUM

The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum on different steps of the metabolism of thiamine (Th), thia mine monophosphate (ThMP) and thiamine pyrophosphate (ThPP) were evalu ated in vivo in rats. CD was carried out by i.p. injection of 5-acetyl pyridine, followed by harmaline and niacinamide. SD was carried out by complete dissection of the peduncles of the left cerebellar hemispher e. Under steady state condition the radioactivity of Th and its phosph oesters was determined in plasma and whole cerebellum after an i.p. in jection of thiazole-[2(14)C]-thiamine (30 mu g:1.25 mu Ci). Analytical data were processed by using an improved mathematical compartmental m odel, which allowed the calculation of fractional rate constants (FRC) , turnover rates (TR) and turnover times (TT). Both CD and SD caused a significant reduction of TR values for Th phosphorylation to ThPP, de phosphorylation of ThPP to ThMP and Th, and ThMP, but not Th, release. TT for all Th compounds were increased compared to controls, indicati ng a general slowing of thiamine metabolism in the deafferented cerebe llum. These results indicate an imbalance in the thiamine metabolism r esulting from the impaired activity of cerebellar neurons. The possibl e implications of the changes in rate of Th compound turnover with res pect to biochemical changes in cerebellar ataxia are discussed.