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Learning, memory and the expression of cholinergic components in mice are modulated by the pesticide chlorpyrifos depending upon age at exposure and apolipoprotein E (APOE) genotype

Journal article
Authors P. Basaure
L. Guardia-Escote
M. Cabre
Fiona Peris-Sampedro
F. Sanchez-Santed
J. L. Domingo
M. T. Colomina
Published in Archives of Toxicology
Volume 93
Issue 3
Pages 693-707
ISSN 0340-5761
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Pages 693-707
Language en
Links dx.doi.org/10.1007/s00204-019-02387...
Keywords Apolipoprotein E, Pesticide, Cholinergic system, Sex differences, Learning, Memory, nicotinic acetylcholine-receptors, pp swedish mice, targeted, replacement, epsilon-4 allele, transgenic mice, behavioral consequences, alzheimers-disease, postnatal exposure, oxidative stress, dietary, exposure, Toxicology, netics, v177, p126, rmany, v22, p545
Subject categories Toxicology, Toxicology, Toxicology

Abstract

Polymorphisms of the apolipoprotein E (APOE) gene differentially affect neurobiological functions and cognitive performance and confer different vulnerabilities to subclinical exposures to chlorpyrifos (CPF), a pesticide used worldwide. The data reported on this topic suggest a complex interaction between cholinergic signaling and the APOE genotype. To gain greater functional insight into this interaction, we evaluated spatial learning and memory and hippocampal cholinergic expression in young apoE3 and apoE4 transgenic mice exposed to CPF. Male and female mice were exposed to CPF at 0 or 1 mg/kg on postnatal days 10-15 and then, exposed to CPF at 0 or 2 mg/kg for 60 days at 5 months of age. At 6 months of age, mice were tested for spatial skills in a Barnes maze. At the end of the task, animals were killed and gene expression of cholinergic components was assessed in the hippocampus. Our results show that apoE4 female mice performed worse in the spatial task, while postnatal CPF impaired escape strategies and spatial memory in apoE3 mice. In turn, CPF in adulthood improved spatial abilities in apoE4 female mice. Regarding gene expression, choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) expression were increased in apoE4 mice. Postnatal exposure to CPF increased ChAT mRNA levels in apoE4 mice, whereas adult exposure to CPF induced changes in acetylcholinesterase-S, alpha 7- and alpha 4-subunit nicotinic receptor expression in apoE4 females. The current findings provide new insights into APOE-dependent cholinergic signaling, which directly affects the response to CPF cholinergic insult, especially in APOE4 subjects.

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Denna text är utskriven från följande webbsida:
http://gu.se/english/research/publication/?publicationId=280536
Utskriftsdatum: 2019-09-20