Publications

This chapter focuses on the cholinergic drug resistance and impaired spatial learning in transgenic mice overexpressing human brain acetylcholinesterase. Appropriate functioning of the cholinergic synapse requires a precise balance of its elements. Important contributors toward this balance are the acetylcholine (ACh) synthesizing enzyme choline acetyltransferase, the hydrolyzing enzyme acetylcholinesterase (AChE), and ACh receptors. Balanced cholinergic neurotransmission is disrupted in several pathological situations. Expression of human AChE under control of the authentic human promoter and first intron is observed in central nervous system neurons of transgenic mice. This expression changed responses to hypothermia-inducing drugs acting on cholinergic and probably serotonergic receptors. In addition, it created a progressive spatial learning and memory impairment. In contrast, the open field behavior of these transgenic animals remained normal. These findings suggest that subtle alterations in the cholinergic balance may cause physiologically observable changes and contribute by itself to the memory deterioration in at least a part of the patients with cholinergic deficits.