Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex
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Purpose: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer’sdisease and have been correlated with memory function. Although regions representing glucose hypometabolism inpatients with Alzheimer’s disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervationand glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changescaused by cholinergic deficits. Materials and Methods: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Results: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the targetquadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normalgroup. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Conclusion: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neurondamage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucosehypometabolism.
Abstract
Purpose: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer’sdisease and have been correlated with memory function. Although regions representing glucose hypometabolism inpatients with Alzheimer’s disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervationand glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changescaused by cholinergic deficits. Materials and Methods: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. Results: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the targetquadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normalgroup. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Conclusion: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neurondamage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucosehypometabolism.
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