Selective inhibition of glial cell metabolism in vivo by fluorocitrate

Abstract

The effect of fluorocitrate on glial and neuronal amino acid metabolism was studied. One nmol of fluorocitrate administered intrastriatally in the rat caused a 95% reduction of glutamine formation from [¹⁴C]acetate, a substrate which enters the glial cells selectively. The metabolism of [¹⁴C]glucose which enters neurons, was unaffected by fluorocitrate treatment except for the glutamine formation. This is evidence that fluorocitrate is a selective inhibitor of the glial Krebs' cycle. [¹⁴C]Citrate and 2-oxoglutarate labelled amino acids in a manner similar to [¹⁴C]acetate, which shows that these substrates are taken up and metabolized by glial cells. Differences in the labelling of γ-aminobutyric acid (GABA) from [¹⁴C]acetate and citrate suggest that astrocytes associated with GABAergic and glutamatergic nerve terminals may differ in their preference for amino acid precursors.