THE EFFECT OF NEURONAL PERTURBATION ON THE UPTAKE OF [F-18] 2-FLUORO-2-DEOXY-D-GLUCOSE IN BRAIN-SLICES OF THE RAT

The positron-emitting radionuclide F-18 was used to label 2-fluoro-2-d eoxy-D-glucose producing [F-18]2-fluoro-2-deoxy-D-glucose ([F-18]FDG), and subsequently applied to sagittally-sectioned brain slices of the rat to evaluate the activity of neurons for up to 7 h in living brain slices. The amount of [F-18]FDG uptake, which is proportional to the a ctivity of neurons, was monitored every 20 min in five representative brain regions: frontal cortex, caudate-putamen. thalamus, hippocampus and cerebellum. The uptake of [F-18]FDG linearly increased with time i n these areas, showing constant glucose utilization. The rate of uptak e was reversibly decreased by tetrodotoxin (TTX) regardless of brain r egion, but some uptake was insensitive to TTX. There was a tendency fo r the uptake to be decreased in Ca2+-free, 5 mM Mg2+ (2 mM EGTA) solut ion, suggesting some remaining functional synapses. Thus in sagittally -sectioned brain slices, most glucose metabolism is dedicated to neuro nal firings and some metabolism to synaptic activities and to other fu nctions of neurons and glial cells. When Cd2+ was applied to brain sli ces at 0.1-1 mM, the curve of [F-18]FDG uptake irreversibly declined, indicating its toxic effect rather than its blocking action of transmi tter release at synapses. The cerebellum was the most sensitive to Cd2 +, and the caudate-putamen was the least sensitive. The present method , therefore, can be also used as a rapid examination system for checki ng neurotoxicity of substances. (C) 1998 Elsevier Science ireland Ltd. All rights reserved.