International Journal of Molecular Sciences

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Dear Colleagues,

Neonicotinoid insecticides are used worldwide, although they have demonstrated toxicity towards beneficial insects such as honeybees. Their effectiveness is predominantly attributed to their high affinity for insect neuronal nicotinic acetylcholine receptors (nAChRs). Mammalian neuronal nAChRs are of major importance because cholinergic synaptic transmission plays a key role in rapid neurotransmission, learning and memory processes, and neurodegenerative diseases. Because of the low agonist effects of neonicotinoid insecticides on mammalian neuronal nAChRs, it has been suggested that they are relatively safe for mammals, including humans. However, several lines of evidence have demonstrated that neonicotinoid insecticides can modulate cholinergic functions through neuronal nAChRs. Major studies on the influence of neonicotinoid insecticides on cholinergic functions have been conducted using nicotine low-affinity homomeric α7 and high-affinity heteromeric α4β2 receptors, as they are highly abundant in the nervous system. Furthermore, neonicotinoids thiamethoxam and clothianidin can activate the release of dopamine in rat striatum. In some contexts, such as neurodegenerative diseases, they can disturb the neuronal distribution or induce oxidative stress, leading to neurotoxicity.

This Special Issue aims to explore the molecular mechanism of action of neonicotinoid insecticides through chemical analyses and toxicology studies, from the molecular to the cellular levels.

Prof. Dr. Steeve Hervé Thany
Guest Editor

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Keywords

neonicotinoids
toxicity
chemistry
mode of action
nicotinic acetylcholine receptors

Published Papers (2 papers)

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Research

10 pages, 967 KiB

Open AccessCommunication

Molecular Mechanism of Action of Cycloxaprid, An Oxabridged cis-Nitromethylene Neonicotinoid

by Yixi Zhang, Xiaoyong Xu, Jingting Wang, Xusheng Shao, Zewen Liu and Zhong Li

Int. J. Mol. Sci. 2023, 24(8), 7511; https://doi.org/10.3390/ijms24087511 - 19 Apr 2023

Viewed by 1025

Abstract

Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity in Hemipteran insect pests. In this study, the action of cycloxaprid was characterized by recombinant receptor Nlα1/rβ2 and cockroach neurons. On Nlα1/β2 in Xenopus oocytes, cycloxaprid acted as a full agonist. The imidacloprid resistance-associated mutation Y151S reduced the I_max of cycloxaprid by 37.0% and increased EC₅₀ values by 1.9-fold, while the I_max of imidacloprid was reduced by 72.0%, and EC₅₀ values increased by 2.3-fold. On cockroach neurons, the maximum currents elicited by cycloxaprid were only 55% of that of acetylcholine, a full agonist, but with close EC₅₀ values of that of trans-neonicotinoids. In addition, cycloxaprid inhibited acetylcholine-evoked currents on insect neurons in a concentration-dependent manner when co-applied with acetylcholine. Cycloxaprid at low concentrations significantly inhibited the activation of nAChRs by acetylcholine, and its inhibition potency at 1 µM was higher than its activation potency on insect neurons. Two action potencies, activation, and inhibition, by cycloxaprid on insect neurons provided an explanation for its high toxicity to insect pests. In summary, as a cis-nitromethylene neonicotinoid, cycloxaprid showed high potency on both recombinant nAChR Nlα1/β2 and cockroach neurons, which guaranteed its high control effects on a variety of insect pests. Full article

(This article belongs to the Special Issue Molecular Mechanism of Action of Neonicotinoid Insecticides 2.0)

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13 pages, 3482 KiB

Open AccessArticle

Reproductive Outbreaks of Sogatella furcifera Mediated by Overexpression of the Nuclear Receptor USP under Pressure from Triflumezopyrim

by Yuming Zhang, Yanwei Ruan, Changwei Gong, Shuirong Zhang, Jingyue Zhang, Yunfeng He, Qiulin Wang, Dan Liu, Jian Pu, Xuemei Liu, Chunxian Jiang and Xuegui Wang

Int. J. Mol. Sci. 2022, 23(22), 13769; https://doi.org/10.3390/ijms232213769 - 9 Nov 2022

Cited by 2 | Viewed by 1334

Abstract

Long-term pesticide-driven selection pressure is one of the main causes of insect outbreaks. In this study, we found that low doses of triflumezopyrim could increase the fecundity of white-backed planthoppers (Sogatella furcifera). By continuously screening 20 generations with a low dose of triflumezopyrim, a triflumezopyrim-resistant strain (Tri-strain, resistance ratio = 20.9-fold) was obtained. The average oviposition quantity and longevity of the Tri-strain (208.77 eggs and 21.31 days, respectively) were significantly higher than those of the susceptible strain (Sus-strain) (164.62 eggs and 17.85 days, respectively). To better understand the mechanism underlying the effects on reproduction, we detected the expression levels of several reproduction-related transcription factors in both the Tri- and Sus-strains. Ultraspiracle (USP) was significantly overexpressed in the Tri-strain. Knockdown of USP by RNAi severely inhibited the moulting process of S. furcifera and disrupted the development of female adult ovaries. Among the potential downstream target genes of USP, Kr-h1 (0.19-fold), Cht8 (0.56-fold) and GPCR A22 (0.31-fold) showed downregulated expression after USP-RNAi. In contrast, the expression of EcR (2.55-fold), which forms heterodimers with USP, was significantly upregulated. Furthermore, RNAi was performed on Kr-h1 in the Tri-strain, and the results show that larval moulting and the development of female adult ovaries were inhibited, consistent with the USP-RNAi results in S. furcifera. These results suggest that the transcription factors USP and Kr-h1 play important roles in the reproductive development of S. furcifera, and overexpression of USP and Kr-h1 in the Tri-resistant strain may result in reproductive outbreaks of pests. Full article

(This article belongs to the Special Issue Molecular Mechanism of Action of Neonicotinoid Insecticides 2.0)

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