Hypercholesterolemia impairs contextual fear conditioning memory formation in female mice: evidence for cholinergic dysfunction. Issue 13 (5th September 2018)

• Record Type: Journal Article
• Authors: Machado, Adriano E.; de Sousa, Guilherme; Mancini, Gianni; Faria, Moacir S.; de Bem, Andreza F.; Moreira, Eduardo L.G.
• Is Part Of: NeuroReport. Volume 29:Issue 13(2018)
• Publication Date: 2018-09-05
• Subjects: donepezil -- fear memory -- hypercholesterolemia -- learning and memory -- scopolamine; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000001091
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : The present study evaluated the effects of hypercholesterolemia in response to conditioned aversive stimuli in mice. Specifically, (a) young (3 months old) and aged (24 months old) female C57Bl/6 mice were fed daily for 4 weeks with a standard rodent diet or an enriched cholesterol diet (ECD) and then subjected to the contextual fear conditioning test. In another experimental set, 3-month-old C576Bl/6 female mice, fed daily during the 4 weeks with the standard rodent diet or ECD, were subjected to the contextual fear conditioning test and received vehicle or scopolamine (0.37 mg/kg; intraperitoneally) immediately after the training session. (b) 12-month-old C576Bl/6 and low-density lipoprotein receptor knockout mice (LDLr −/− ) female mice were subjected to the contextual fear conditioning test. In another experimental set, they were subjected to the contextual fear conditioning test and received vehicle or donepezil (3.0 mg/kg; intraperitoneally) immediately after the training session. The present results show that (a) the ECD specifically impaired retrieval of contextual fear memory in aged mice; (b) an ineffective dose of scopolamine impaired fear memory consolidation in young mice fed the ECD; (c) LDLr −/− mice presented impaired contextual fear memory retrieval; and (d) boosting cholinergic neurotransmission with a single donepezil administration at the consolidation window led to improved fear memory consolidation in LDLr −/− mice. These findings suggest that high levels of cholesterol induced by either an ECD or a genetic deletion of LDLr decreased freezing behavior on the contextual fear conditioning test, which seemed to involve dysfunction of the cholinergic system.