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- Basaure, P., et al.
(författare)
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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
- 2019
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 93:3, s. 693-707
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Tidskriftsartikel (refereegranskat)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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- Guardia-Escote, L., et al.
(författare)
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APOE genetic background and sex confer different vulnerabilities to postnatal chlorpyrifos exposure and modulate the response to cholinergic drugs
- 2019
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328. ; 376
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF) is an extensively used organophosphate pesticide. Exposure to CPF has been related to neurobehavioral disorders, particularly during neurodevelopment. Apolipoprotein E (apoE) is a lipid and cholesterol carrier and a susceptibility factor for cognitive impairment which can influence the response to toxic exposures. The study was aimed at assessing the effects of postnatal exposure to CPF on object recognition memory and its modulation by sex and APOE genotype. Human apoE3 and apoE4 targeted replacement mice and C57BL/6 mice were postnatally exposed to 0 or 1 mg/kg/day of CPF. Recognition memory was evaluated in an Object Recognition Test (ORT). In order to study the contribution of cholinergic and GABAergic neurotransmitter systems to recognition memory, a pharmacological challenge was included. Sex, genotype and postnatal exposure to CPF were key factors throughout the testing period. Specifically, CPF increased exploratory behavior and impaired discrimination performance. We observed that administering scopolamine, a cholinergic antagonist, was detrimental to recognition memory. However, discrimination in C57BL/6 and apoE4 males improved with the administration of the cholinergic agonist rivastigmine, but the same drug worsened retention in apoE4 females. Finally, the GABAergic agonist alprazolam altered performance in a sex- and genotype-dependent manner. Overall, these results suggest complex interactions between sex, APOE genotype and postnatal CPF exposure and indicate a different functioning of both the cholinergic and GABAergic neurotransmitter system between groups. © 2019 Elsevier B.V.
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- Peris-Sampedro, Fiona, et al.
(författare)
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Impact of Free-Choice Diets High in Fat and Different Sugars on Metabolic Outcome and Anxiety-Like Behavior in Rats
- 2019
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 27:3, s. 409-419
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Tidskriftsartikel (refereegranskat)abstract
- Objective Rats were exposed to free-choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences and impact on locomotor activity and anxiety-like behavior were explored. Methods For 3 weeks, 7-week-old male rats were offered either chow only or free-choice high-fat diets differing in their added sugar: no sugar, sucrose, or glucose. In a second experiment, after 2 weeks on the diets, rats were switched from high sucrose to high glucose for two additional weeks. Metabolic end points included body weight, food intake, food choice, glycemic control, metabolic hormones, fat pad weight, brown adipose tissue weight, and gene expression. Behavioral analysis included locomotor and anxiety-like activity in the open field and elevated plus maze. Results Both sugar diets enhanced adiposity and induced hyperphagia, favoring unhealthier dietary selection above that of the control diets (chow or free-choice high-fat with no sugar). Despite isocaloric intake in the sugar-containing diets, offering glucose instead of sucrose was associated with improved insulin sensitivity. The sugar-containing diets reduced activity (but with movements of increased velocity) and induced an anxiety-like phenotype. Conclusions Although free-choice diets negatively impacted on metabolism and anxiety-like behavior, replacing sucrose with glucose improved insulin sensitivity and may therefore be better for health.
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