An Overview on the Effect of Neonicotinoid Insecticides on Mammalian Cholinergic Functions through the Activation of Neuronal Nicotinic Acetylcholine Receptors

Houchat, Jean-Noël; Cartereau, Alison; Mauff, Anaïs Le; Taillebois, Emiliane; Thany, Steeve Hervé

doi:10.3390/ijerph17093222

Cited by 41 publications

(20 citation statements)

References 74 publications

(89 reference statements)

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“…Neonicotinoids (NNs) are a recent class of insecticides with a selective agonistic action on the insect nicotinic acetylcholine receptors (nAChRs) and a low affinity for mammalian nAChRs receptors [ 1 ]. Thus, they have been considered for replacement of classical insecticides, so that they accounted for more than 25% of the global insecticides market in 2014 [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

et al. 2021

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Thiacloprid (TCP) is a widely used neonicotinoid insecticide with a probable toxic hazard to animals and human beings. This hazard has intensified the demand for natural compounds to alleviate the expected toxic insults. This study aimed at determining whether astaxanthin (ASX) could mitigate the hepatotoxic effect of TCP and diminish its suppressive effect on immune responses in rats. Animals received TCP by gavage at 62.1 mg/kg (1/10th LD50) with or without ASX at 40 mg/kg for 60 days. Intoxicated rats showed modulation of serum transaminases and protein profiles. The hemagglutination antibody titer to sheep red blood cells (SRBC) and the number of plaque-forming cells in the spleen were reduced. The cell-mediated immunity and phagocytosis were suppressed, while serum interleukins IL-1β, IL-6, and IL-10 were elevated. Additionally, malondialdehyde, nitric oxide, and 8-hydroxy-2′-deoxyguanosine levels were increased in the liver, spleen, and thymus, with depletion of glutathione and suppression of superoxide dismutase and catalase activities. The expressions of inducible nitric oxide synthase and the high mobility group box protein 1 genes were upregulated with histomorphological alterations in the aforementioned organs. Cotreatment with ASX markedly ameliorated the toxic effects of TCP, and all markers showed a regression trend towards control values. Collectively, our data suggest that the protective effects of ASX on the liver and immune system of TCP-treated animals depend upon improving the antioxidant status and relieving the inflammatory response, and thus it may be used as a promising therapeutic agent to provide superior hepato- and immunoprotection.

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Section: Introductionmentioning

confidence: 99%

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

et al. 2021

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“…Homomeric α7 and heterometric α4β2 receptors are most abundant in the nervous system; each subtype has its unique activation, agonist selectivity, channel conductance, and desensitization properties ( Houchat et al, 2020 ). Activation of α4β2nAChRs triggers slowly decaying nicotinic currents ( Matsubayashi et al, 2004 ), while α7 subtype is distinguished by its rapid desensitization ( Couturier et al, 1990 ; Seguela et al, 1993 ).…”

Section: Discussionmentioning

confidence: 99%

Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking

et al. 2020

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Inhibition of Ras farnesylation in acute has been found to upregulate the α7 nicotinic acetylcholine receptor (α7nAChR) activity. This study was carried out to investigate the effect of chronic administration for 7 days of farnesyl transferase inhibitor lonafarnib (50 mg/kg, intraperitoneally injected) to male mice on the expression and activity of α7nAChR in hippocampal CA1 pyramidal cells. Herein, we show that lonafarnib dose dependently enhances the amplitude of ACh-evoked inward currents (IACh), owning to the increased α7nAChR expression and membrane trafficking. Lonafarnib inhibited phosphorylation of c-Jun and JNK, which was related to DNA methylation. In addition, reduced DNA methyltransferase 1 (DNMT1) expression was observed in lonafarnib-treated mice, which was reversed by JNK activator. Lonafarnib-upregulated expression of α7nAChR was mimicked by DNMT inhibitor, and repressed by JNK activator. However, only inhibited DNA methylation did not affect IACh, and the JNK activator partially decreased the lonafarnib-upregulated IACh. On the other hand, lonafarnib also increased the membrane expression of α7nAChR, which was partially inhibited by JNK activator or CaMKII inhibitor, without changes in the α7nAChR phosphorylation. CaMKII inhibitor had no effect on the expression of α7nAChR. Lonafarnib-enhanced spatial memory of mice was also partially blocked by JNK activator or CaMKII inhibitor. These results suggest that Ras inhibition increases α7nAChR expression through depressed DNA methylation of CHRNA7 via Ras-c-Jun-JNK pathway, increases the membrane expression of α7nAChR resulting in part from the enhanced CaMKII pathway and total expression of this receptor, and consequently enhances the spatial memory.

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“…On the other hand, protonated nicotinoids command cation-π binding to the vertebrate nAChR receptor. These marked differences due to low affinity for vertebrates relative to insect nicotinic receptors catapults neonicotinoids to having favorable toxicological profiles [39].…”

Section: Interaction and Selectivity Mechanisms Of Neonicotinoid Insecticidesmentioning

confidence: 99%

Physiological Effects of Neonicotinoid Insecticides on Non-Target Aquatic Animals—An Updated Review

Malhotra

Chen

Huang

et al. 2021

IJMS

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In this paper, we review the effects of large-scale neonicotinoid contaminations in the aquatic environment on non-target aquatic invertebrate and vertebrate species. These aquatic species are the fauna widely exposed to environmental changes and chemical accumulation in bodies of water. Neonicotinoids are insecticides that target the nicotinic type acetylcholine receptors (nAChRs) in the central nervous systems (CNS) and are considered selective neurotoxins for insects. However, studies on their physiologic impacts and interactions with non-target species are limited. In researches dedicated to exploring physiologic and toxic outcomes of neonicotinoids, studies relating to the effects on vertebrate species represent a minority case compared to invertebrate species. For aquatic species, the known effects of neonicotinoids are described in the level of organismal, behavioral, genetic and physiologic toxicities. Toxicological studies were reported based on the environment of bodies of water, temperature, salinity and several other factors. There exists a knowledge gap on the relationship between toxicity outcomes to regulatory risk valuation. It has been a general observation among studies that neonicotinoid insecticides demonstrate significant toxicity to an extensive variety of invertebrates. Comprehensive analysis of data points to a generalization that field-realistic and laboratory exposures could result in different or non-comparable results in some cases. Aquatic invertebrates perform important roles in balancing a healthy ecosystem, thus rapid screening strategies are necessary to verify physiologic and toxicological impacts. So far, much of the studies describing field tests on non-target species are inadequate and in many cases, obsolete. Considering the current literature, this review addresses important information gaps relating to the impacts of neonicotinoids on the environment and spring forward policies, avoiding adverse biological and ecological effects on a range of non-target aquatic species which might further impair the whole of the aquatic ecological web.

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An Overview on the Effect of Neonicotinoid Insecticides on Mammalian Cholinergic Functions through the Activation of Neuronal Nicotinic Acetylcholine Receptors

Cited by 41 publications

References 74 publications

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

Astaxanthin Mitigates Thiacloprid-Induced Liver Injury and Immunotoxicity in Male Rats

Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking

Physiological Effects of Neonicotinoid Insecticides on Non-Target Aquatic Animals—An Updated Review

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