The effects of apolipoprotein E deficiency on brain cholinergic neurons

Previous studies utilizing apolipoprotein E (apoE)-deficient mice revealed distinct decreases in the levels of cholinergic synaptic markers of project ing basal forebrain cholinergic neurons and no such alterations in other br ain cholinergic systems. In order to investigate the mechanisms underlying these neuron-specific cholinergic effects, primary neuronal cultures From a poE-deficient and control mice were prepared and characterized. These inclu de basal forebrain cultures, which are enriched in projecting cholinergic n eurons, and cortical cultures, which contain cholinergic interneurons. The levels of cholinergic nerve terminals in these cultures were assessed by li gand binding measurements of the levels of the vesicular acetylcholine tran sporter (VAChT). This revealed that basal forebrain cultures of apoE-defici ent mice contain markedly lower VAChT levels (similar to 50%) than do contr ol cultures, but that VAChT levels of the corresponding cortical cultures o f the apoE-deficient and control mice were the same. Time course studies re vealed that VAChT levels of the basal forebrain cultures increased with cul ture ae, but that the relative reduction in VAChT levels of the apoE-defici ent cholinergic neurons was unaltered and was the same for freshly prepared and for 96 h old cultures. These in vivo observations are in accordance wi th the in vivo findings and suggest that projecting basal forebrain choline rgic neurons, but not cholinergic interneurons, are markedly dependent on a poE and that similar mechanisms mediate the in vivo and in vitro effects of apoE deficiency on cholinergic function. (C) 1999 ISDN. Published by Elsev ier Science Ltd. All rights reserved.