Emerging Pharmacological Properties of Cholinergic Synaptic Transmission: Comparison between Mammalian and Insect Synaptic and Extrasynaptic Nicotinic Receptors

Acetylcholine (ACh) is probably the oldest signalling neurotransmitter which appeared in evolution before the nervous system. It is present in bacteria, algae, protozoa and plants. In insects and mammals it is involved in cell-to-cell communications in various neuronal and non-neuronal tissues. The discovery of nicotinic acetylcholine receptors (nAChRs) as the main receptors involved in rapid cholinergic neurotransmission has helped to understand the role of ACh at synaptic level. Recently, several lines of evidence have indicated that extrasynaptically expressed nAChRs display distinct pharmacological properties from the ones expressed at synaptic level. The role of both nAChRs at insect extrasynaptic and/or synaptic levels has been underestimated due to the lack of pharmacological tools to identify different nicotinic receptor subtypes. In the present review, we summarize recent electrophysiological and pharmacological studies on the extrasynaptic and synaptic differences between insect and mammalian nAChR subtypes and we discuss on the pharmacological impact of several drugs such as neonicotinoid insecticides targeting these receptors. In fact, nAChRs are involved in a wide range of pathophysiological processes such as epilepsy, pain and a wide range of neurodegenerative and psychiatric disorders. In addition, they are the target sites of neonicotinoid insecticides which are known to act as nicotinic agonists causing severe poisoning in insects and mammals

Identification of cholinergic synaptic transmission in the insect nervous system

A major criteria initially used to localize cholinergic neuronal elements in nervous systems tissues that involve acetylcholine (ACh) as neurotransmitter is mainly based on immunochemical studies using choline acetyltransferase (ChAT), an enzyme which catalyzes ACh biosynthesis and the ACh degradative enzyme named acetylcholinesterase (AChE). Immunochemical studies using anti-ChAT monoclonal antibody have allowed the identification of neuronal processes and few types of cell somata that contain ChAT protein. In situ hybridization using cRNA probes to ChAT or AChE messenger RNA have brought new approaches to further identify cell bodies transcribing the ChAT or AChE genes. Combined application of all these techniques reveals a widespread expression of ChAT and AChE activities in the insect central nervous system and peripheral sensory neurons which implicates ACh as a key neurotransmitter. The discovery of the snake toxin alpha-bungatoxin has helped to identify nicotinic acetylcholine receptors (nAChRs). In fact, nicotine when applied to insect neurons, resulted in the generation of an inward current through the activation of nicotinic receptors which were blocked by alpha-bungarotoxin. Thus, insect nAChRs have been divided into two categories, sensitive and insensitive to this snake toxin. Up to now, the recent characterization and distribution pattern of insect nAChR subunits and the biochemical evidence that the insect central nervous system contains different classes of cholinergic receptors indicated that ACh is involved in several sensory pathways

Des insecticides plus sélectifs

La découverte d\u27un gène spécifique élargit les voies de recherche pouvant permettre de réduire les "dommages collatéraux" des insecticides

Assessment of Knowledge on Metal Trace Element Concentrations and Metallothionein Biomarkers in Cetaceans

Cetaceans are recognized as bioindicators of pollution in oceans. These marine mammals are final trophic chain consumers and easily accumulate pollutants. For example, metals are abundant in oceans and commonly found in the cetacean tissues. Metallothioneins (MTs) are small non-enzyme proteins involved in metal cell regulation and are essential in many cellular processes (cell proliferation, redox balance, etc.). Thus, the MT levels and the concentrations of metals in cetacean tissue are positively correlated. Four types of metallothioneins (MT1, 2, 3, and 4) are found in mammals, which may have a distinct expression in tissues. Surprisingly, only a few genes or mRNA-encoding metallothioneins are characterized in cetaceans; molecular studies are focused on MT quantification, using biochemical methods. Thus, we characterized, in transcriptomic and genomic data, more than 200 complete sequences of metallothioneins (mt1, 2, 3, and 4) in cetacean species to study their structural variability and to propose to the scientific research community Mt genes dataset to develop in future molecular approaches which will study the four types of metallothioneins in diversified organs (brain, gonad, intestine, kidney, stomach, etc.).Fil: Leignel, Vincent. Le Mans Université.; FranciaFil: Pillot, Louis. Le Mans Université.; FranciaFil: Gerpe, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Caurant, Florence. La Rochelle University; Franci

Pest Insect Olfaction in an Insecticide-Contaminated Environment: Info-Disruption or Hormesis Effect

Most animals, including pest insects, live in an “odor world” and depend strongly on chemical stimuli to get information on their biotic and abiotic environment. Although integrated pest management strategies including the use of insect growth regulators (IGRs) are increasingly developed, most insect pest treatments rely on neurotoxic chemicals. These molecules are known to disrupt synaptic transmission, affecting therefore sensory systems. The wide-spread use of neurotoxic insecticides and the growing use of IGRs result in residual accumulation of low concentrations in the environment. These insecticide residues could act as an “info-disruptor” by modifying the chemical communication system, and therefore decrease chances of reproduction in target insects. However, residues can also induce a non-expected hormesis effect by enhancing reproduction abilities. Low insecticide doses might thus induce adaptive processes in the olfactory pathway of target insects, favoring the development of resistance. The effect of sublethal doses of insecticides has mainly been studied in beneficial insects such as honeybees. We review here what is known on the effects of sublethal doses of insecticides on the olfactory system of insect pests

Injection of insect membrane in Xenopus oocyte: An original method for the pharmacological characterization of neonicotinoid insecticides

Insect nicotinic acetylcholine receptors (nAChRs) represent a major target of insecticides, belonging to the neonicotinoid family. However, the pharmacological profile of native nAChRs is poorly documented, mainly because of a lack of knowledge of their subunit stoichiometry, their tissue distribution and the weak access to nAChR-expressing cells. In addition, the expression of insect nAChRs in heterologous systems remains hard to achieve. Therefore, the structure–activity characterization of nAChR-targeting insecticides is made difficult. The objective of the present study was to characterize insect nAChRs by an electrophysiological approach in a heterologous system naturally devoid of these receptors to allow a molecular/cellular investigation of the mode of action of neonicotinoids