In vivo study of the kinetics of thiamine and its phosphoesters in the deafferented rat cerebellum

A. Nauti, C. Patrini, C. Reggiani, A. Merighi, R. Bellazzi, G. Rindi

Research output: Contribution to journalArticle

Abstract

The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum on different steps of the metabolism of thiamine (Th), thiamine monophosphate (ThMP) and thiamine pyrophosphate (ThPP) were evaluated in vivo in rats. CD was carried out by i.p. injection of 3-acetylpyridine, followed by harmaline and niacinamide. SD was carried out by complete dissection of the peduncles of the left cerebellar hemisphere. Under steady state condition the radioactivity of Th and its phosphoesters was determined in plasma and whole cerebellum after an i.p. injection of thiazole-[214C]-thiamine (30 μg:1.25 μCi). Analytical data were processed by using an improved mathematical compartmental model, 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, dephosphorylation of ThPP to ThMP and Th, and ThMP, but not Th, release. TT for all Th compounds were increased compared to controls, indicating a general slowing of thiamine metabolism in the deafferented cerebellum. These results indicate an imbalance in the thiamine metabolism resulting from the impaired activity of cerebellar neurons. The possible implications of the changes in rate of Th compound turnover with respect to biochemical changes in cerebellar ataxia are discussed.

Original languageEnglish
Pages (from-to)145-159
Number of pages15
JournalMetabolic Brain Disease
Volume12
Issue number2
DOIs
Publication statusPublished - 1997

Keywords

  • Cerebellar deafferentation
  • Compartmental model
  • Kinetics in vivo
  • Nervous system
  • Thiamine
  • Thiamine phosphoesters

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Neuroscience(all)

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