Glucose metabolism in cholinoceptive cortical rat brain regions after basal forebrain cholinergic lesion

To address the question whether the changes in cortical glucose metabolism observed in patients with Alzheimer's disease are interrelated with, or con sequences of. basal forebrain cholinergic cell loss, an experimental approa ch was employed to produce cortical cholinergic dysfunction in rat brain by administration of the cholinergic immunotoxin 192IgG-saporin. [C-14]D-gluc ose utilization in brain homogenates, D-glucose-displaceable [H-3]cytochala sin B binding to glucose transporters (GLUT), Northern and Western analyses , as well as bl vivo [C-14]2-deoxyglucose autoradiography were used to quan tify the regional glucose metabolism. Basal forebrain cholinergic lesion resulted in transient increases in gluco se transporter binding in cortical regions displaying reduced acetylcholine sterase activity, already detectable seven days after lesion with peak valu es around 30 days post lesion. Western analysis revealed that the changes i n total glucose transporter binding are mainly due to changes in the GLUT3 subtype only, while the levels of GLUT1 and GLUT3 mRNA (Northern analysis) were not affected by cholinergic lesion. Both immunocytochemistry and in si tu hybridization demonstrated preferential localizations of GLUT1 on brain capillaries and GLUT3 on neurons, respectively. A lesion-induced transient decrease in [C-14]D-glucose utilization seven days post lesion was detected in the lesion site, whereas cholinoceptive cortical regions were not affec ted. In vivo [C-14]deoxyglucose uptake was transiently increased in cholino ceptive cortical regions and in the Lesion site being highest between three to seven days after lesion. The cholinergic lesion-induced transient up-regulation of cortical glucose transporters and deoxyglucose uptake reflects an increased glucose demand i n regions depleted by acetylcholine suggesting functional links between cor tical cholinergic activity and glucose metabolism in cholinoceptive target regions. (C) 1999 ISDN. Published by Elsevier Science Ltd. All rights reser ved.