Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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

Fingerprint

Apolipoproteins E
Cholinergic Receptors
Acetylcholine
Scopolamine Hydrobromide
Muscarinic Receptors
Alzheimer Disease
Classical Conditioning
Reaction Time
Inbred C57BL Mouse
Cholinergic Agents
Genotype

Keywords

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

ASJC Scopus subject areas

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

Cite this

Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E. / Siegel, Jessica A.; Benice, Theodore S.; Van Meer, Peter; Park, Byung; Raber, Jacob.

In: Neurobiology of Aging, Vol. 32, No. 1, 01.2011, p. 75-84.

Research output: Contribution to journalArticle

Siegel, Jessica A. ; Benice, Theodore S. ; Van Meer, Peter ; Park, Byung ; Raber, Jacob. / Acetylcholine receptor and behavioral deficits in mice lacking apolipoprotein E. In: Neurobiology of Aging. 2011 ; Vol. 32, No. 1. pp. 75-84.
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