Funções motoras em camundongos deficientes do transportador vesicular de acetilcolina (VAChT)

Abstract

Acetylcholine (ACh)mediated neurotransmission has a crucialrole in the control of movement. Release of ACh depends on its storagein synaptic vesicles, a step controlled by the activity of the VAChT. Wedeveloped a genetically altered strain of mice with reduced expression ofthis transporter. Heterozygous (VAChT KDHET) and homozygous (VAChTKDHOM) knockdown mice have 45 and 65% decrease in VAChT protein.To evaluate whether VAChT deficiency may affect motor functions, weused the following tasks: grip force, wire hang and treadmill. Motorlearning was measured on the rotarod. We were unable to detect anyalteration in the grip force, wire hang and treadmill tests in VAChT KDHETmice; however VAChT KDHOM mice were significantly impaired in allthree tasks. Reduced grip strength in VAChT KDHOM mice was readilyreversed by prior injection of galantamine. Moreover, motor learningperformance on the accelerating rotarod task by VAChT KDHET mice wasworse than for wild type controls. Our results demonstrate that differentlevels of cholinergic hypofunction may causes distinct types of motorabnormality. VAChT KDHOM shows a myastenic profile, while VAChTxi KDHET mice presented a decrease in motor learning with normal motor function. These genetically modified mice may represent a novel model system for investigation of motor control and congenital myasthenic syndromes.