Improvement of cholinergic function during normal and pathological aging

Abstract

Cholinergic neurons produce the neurotransmitter acetylcholine and are essential to critical brain functions, including motor function, learning and memory. The vesicular acetylcholine transporter (VAChT) is expressed by cholinergic neurons and packages acetylcholine into vesicles to prepare its release to the synaptic cleft. Here, we report that increasing levels of VAChT is associated with neurochemical alterations that may improve motor behaviour and cognitive decline during normal and pathological aging. Using RT‐PCR, immunohistochemistry, and western blot, we show that B6.Cg‐Tg(RP23–268L19‐EGFP)2Mik/J mice exhibit enhanced VAChT mRNA and protein expression. These changes were sufficient to enhance acetylcholine release at cholinergic terminals, and elicit changes in behavioural functions including spontaneous and novelty‐induced activity and measures of cognition. Mechanisms for these behavioural features will be explored. Taken together, this study contributes to our fundamental understanding of cholinergic regulation, specifically in response to increased VAChT expression, and may implicate VAChT as a target to maintain adequate cholinergic function during aging.