Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E.
Apolipoprotein E (apoE) is involved in the risk to develop sporadic Alzheimer's disease (AD). Since impaired central acetylcholine (ACh) function is a hallmark of AD, apoE may influence ACh function by modulating muscarinic ACh receptors (mAChRs). To test this hypothesis, mAChR binding was measured in mice lacking apoE and wild type C57BL/6J mice. Mice were also tested on the pre-pulse inhibition, delay eyeblink classical conditioning, and 5-choice serial reaction time tasks (5-SRTT), which are all modulated by ACh transmission. Mice were also given scopolamine to challenge central mAChR function. Compared to wild type mice, mice lacking apoE had reduced number of cortical and hippocampal mAChRs. Scopolamine had a small effect on delay eyeblink classical conditioning in wild type mice but a large effect in mice lacking apoE. Mice lacking apoE were also unable to acquire performance on the 5-SRTT. These results support a role for apoE in ACh function and suggest that modulation of cortical and hippocampal mAChRs might contribute to genotype differences in scopolamine sensitivity and task acquisition. Impaired apoE functioning may result in cholinergic deficits that contribute to the cognitive impairments seen in AD.
Siegel
Jessica A
JA
Department of Behavioral Neuroscience, Oregon Health & Science University, 8131 SW Sam Jackson Park Road, Portland, OR 97239, USA. siegelj@ohsu.edu
Benice
Theodore S
TS
Van Meer
Peter
P
Park
Byung S
BS
Raber
Jacob
J
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001526:Behavioral Symptoms / Q000097:blood / Q000235:genetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012022:Reflex, Acoustic / Q000187:drug effects / Q000235:genetics; D012601:Scopolamine / Q000494:pharmacology
D001057:Apolipoproteins E; D018680:Cholinergic Antagonists; D011976:Receptors, Muscarinic; D012601:Scopolamine; D003345:Corticosterone