USE OF FLUOROCITRATE AND FLUOROACETATE IN THE STUDY OF BRAIN METABOLISM

Fluoroacetate and its toxic metabolite fluorocitrate cause inhibition of aconitase. In brain tissue, both substances are preferentially take n up by glial cells and leads to inhibition of the glial TCA cycle. It is important to realise, however, that the glia-specificity of these compounds depends both on the dosage and on the model used. The glia-i nhibitory effect of fluorocitrate as obtained by intracerebral microin jection in vivo is reversible within 24 h. A substantial inhibition of the glial TCA cycle by systemic administration of fluoroacetate requi res a lethal dose. Inhibition of the glial aconitase leads to accumula tion of citrate and to a reduction in the formation of glutamine. Wher eas the former is likely to be responsible for the main toxic effect o f these compounds possibly by chelation of free calcium ions, it is th e latter that has received most attention in the study of glial-neuron al interactions, since glutamine is an important precursor for transmi tter glutamate and GABA. (C) 1997 Wiley-Liss, Inc.