Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E

Jessica A. Siegel, Theodore S. Benice, Peter Van Meer, Byung S. Park, Jacob Raber

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)75-84
Number of pages10
JournalNeurobiology of Aging
Volume32
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Acetylcholine
  • Alzheimer's disease
  • Apolipoprotein E
  • Attention
  • Muscarinic
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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