title: Binary mixtures of neonicotinoids show different transcriptional changes than single neonicotinoids in honeybees (Apis mellifera).
abstract: Among the many factors responsible for the decline of bee populations are plant protection products such as neonicotinoids. In general, bees are exposed to not only one but mixtures of such chemicals. At environmental realistic concentrations neonicotinoids may display negative effects on the immune system, foraging activity, learning and memory formation of bees. Neonicotinoids induce alterations of gene transcripts such as nicotinic acetylcholine receptor (nAChR) subunits, vitellogenin, genes of the immune system and genes linked to memory formation. While previous studies focused on individual compounds, the effect of neonicotinoid mixtures in bees is poorly known. Here we investigated the effects of neonicotinoids acetamiprid, clothianidin, imidacloprid and thiamethoxam as single compounds, and binary mixtures thereof in honeybees. We determined transcriptional changes of nAChR subunits and vitellogenin in the brain of experimentally exposed honeybees after exposure up to 72 h. Exposure concentrations were selected on the basis of lowest effect concentrations of the single compounds. Transcriptional induction of nAChRs and vitellogenin was strongest for thiamethoxam, and weakest for acetamiprid. To a large extent, binary mixtures did not show additive transcriptional inductions but they were less than additive. Our data suggest that the joint transcriptional activity of neonicotinoids cannot be explained by concentration addition. The in vivo effects are not only governed by agonistic interaction with nAChRs alone, but are more complex as a result of interactions with other pathways as well. Further studies are needed to investigate the physiological joint effects of mixtures of neonicotinoids and other plant protection products on bees to better understand their joint effects.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Christen
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland; University Basel, Department of Pharmaceutical Sciences, Institute of Molecular and System Toxicology, CH-4056 Basel, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Bachofer
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland; Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Environmental System Sciences, Institute of Biogeochemistry and Pollution Dynamics, CH-8092 Zürich, Switzerland. Electronic address: karl.fent@bluewin.ch.
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000818:Animals; D001516:Bees / Q000187:drug effects* / Q000235:genetics; D004347:Drug Interactions; D006146:Guanidines / Q000633:toxicity; D007093:Imidazoles / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000633:toxicity; D010078:Oxazines / Q000633:toxicity; D011725:Pyridines / Q000633:toxicity; D011978:Receptors, Nicotinic / Q000235:genetics; D000077922:Thiamethoxam; D013844:Thiazoles / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D006146:Guanidines; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D010078:Oxazines; D011725:Pyridines; D011978:Receptors, Nicotinic; D013844:Thiazoles; C480342:clothianidin; C082359:imidacloprid; C464485:acetamiprid; D000077922:Thiamethoxam
keywords: Honeybees; Mixture activity; Neonicotinoids; Nicotinic acetylcholine receptors; Transcription analysis; Vitellogenin