Cited by 74Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchCholinesterase and Neurodegenerative Diseases

Cholinergic systems and long-term potentiation in memory-impaired apolipoprotein E-deficient mice

Krzywkowski, P., Ghribi, O., Gagné, J., Chabot, C., Kar, S., Rochford, J., Massicotte, G., Poirier, J.·1999·Neuroscience

Abstract

Impairments in cholinergic neurotransmitter systems of the basal forebrain are a hallmark of Alzheimer's disease pathophysiology. The presence of the epsilon4 allele of apolipoprotein E was recently implicated as a major risk factor in both familial and sporadic Alzheimer's disease. The present study examined the integrity of cholinergic and non-cholinergic systems in apolipoprotein E-deficient, memory-impaired mice. Choline acetyltransferase activity, hippocampal acetylcholine release, nicotinic and muscarinic (M1 and M2) receptor binding sites and acetylcholinesterase cell or terminal density showed no signs of alteration in either three-month or 9.5-month-old apolipoprotein E-deficient mice compared to controls. In contrast, long-term potentiation was found to be markedly reduced in these mice, but increases in the strength of stimulation induced the same level of long-term potentiation as that observed in controls. These alterations did not appear to be the consequence of modifications in the binding properties of glutamatergic receptors (N-methyl-D-aspartate and [RS]-alpha-amino-3-hydroxy-5-methylisoxazole propionic acid) but from defective regulation of the (RS)-alpha-amino-3-hydroxy-5-methylisoxazole propionic acid receptor by phospholipase A2 activity. These results support the notion that apolipoprotein E plays a fundamental role in neuronal plasticity, which could in turn affect cognitive performance through imbalances in extra- and intracellular lipid homeostasis.

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Crossref · 10.1016/s0306-4522(99)00061-5

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Authors
Krzywkowski, P., Ghribi, O., Gagné, J., Chabot, C., Kar, S., Rochford, J., Massicotte, G., & Poirier, J.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • Université du Québec à Trois-Rivières (CA)
Corresponding author
Poirier, J.
Venue
Neuroscience
Publisher
Elsevier BV
Published
1999-06
Volume
92
Issue
4
Pages
1273-1286
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2043012963
Cited by
74
References
81
Citations by year
2025: 1 · 2024: 2 · 2017: 1 · 2016: 1 · 2014: 5 · 2013: 7 · 2012: 1
FWCI
3.73
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
Natural Sciences and Engineering Research Council of Canada
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
apolipoprotein E deficiency, APOE ε4, Alzheimer's disease, cholinergic system, long-term potentiation, memory impairment, hippocampus, nicotinic acetylcholine receptors, muscarinic receptors, acetylcholinesterase, choline acetyltransferase, glutamate receptors, NMDA receptor, AMPA receptors, phospholipase A2, neuroplasticity, lipid homeostasis, basal forebrain
MeSH terms
Acetylcholine, Acetylcholinesterase, Animals, Apolipoproteins E, Autoradiography, Brain, Choline O-Acetyltransferase, Histocytochemistry, Memory Disorders, Mice, Inbred C57BL, Parasympathetic Nervous System, Phospholipases A, Receptors, Muscarinic, Receptors, Nicotinic, Long-Term Potentiation, Mice, Knockout, Glutamic Acid, Maze Learning, Mice, Phospholipases A2

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