Decreased vesicular acetylcholine transporter related to memory deficits in epilepsy: A [ 18 18 F] VAT positron emission tomography brain imaging study

摘要

Summary Objective Vesicular acetylcholine transporter ( VAC hT) is a rate‐limiting factor for synaptic acetylcholine transport. Our study focused on whether [ 18 F] VAT , a novel positron emission tomography ( PET ) tracer, could be used in detecting cognitive deficits in epilepsy. Methods Morris water maze test was used to evaluate learning and memory deficits in pilocarpine‐induced chronic epilepsy rats 12 weeks after status epilepticus. Interictal [ 18 F] VAT PET was performed 13 weeks after status epilepticus to evaluate the level of VAC hT in cholinergic pathways compared with [ 18 F] fluorodeoxyglucose PET . The association between VAC hT levels and memory measures was analyzed. Neuropathological tests were performed. Results Epileptic rats exhibited significant memory deficits in Morris water maze test. [ 18 F] VAT uptake decreased in septum, hippocampus, thalamus, and basal forebrain, and correlated to memory function. Of note, the level of VAC hT in basal forebrain significantly decreased, yet no glucose hypometabolism was detected. Immunofluorescence and Western blot demonstrated decreased expression of VAC hT in hippocampus and basal forebrain in the epilepsy group, but no change of expression of acetyltransferase or activity of acetylcholinesterase was detected. Significance [ 18 F] VAT PET is a promising method to test the level of VAC hT as a valuable biomarker for memory deficits in pilocarpine‐induced chronic epileptic rats.