The effect of neuronal perturbation on the uptake of [ 18F]2-fluoro-2-deoxy-D-glucose in brain slices of the rat

Abstract

The positron-emitting radionuclide 18F was used to label 2-fluoro-2-deoxy-D-glucose producing [ 18F]2-fluoro-2-deoxy-D-glucose ([ 18F]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 [ 18F]FDG uptake, which is proportional to the activity of neurons, was monitored every 20 min in five representative brain regions: frontal cortex, caudate-putamen, thalamus, hippocampus and cerebellum. The uptake of [ 18F]FDG linearly increased with time in these areas, showing constant glucose utilization. The rate of uptake was reversibly decreased by tetrodotoxin (TTX) regardless of brain region, but some uptake was insensitive to TTX. There was a tendency for the uptake to be decreased in Ca 2+-free, 5 mM Mg 2+ (2 mM EGTA) solution, suggesting some remaining functional synapses. Thus in sagittally-sectioned brain slices, most glucose metabolism is dedicated to neuronal firings and some metabolism to synaptic activities and to other functions of neurons and glial cells. When Cd 2+ was applied to brain slices at 0.1–1 mM, the curve of [ 18F]FDG uptake irreversibly declined, indicating its toxic effect rather than its blocking action of transmitter release at synapses. The cerebellum was the most sensitive to Cd 2+, and the caudate-putamen was the least sensitive. The present method, therefore, can be also used as a rapid examination system for checking neurotoxicity of substances.