Acute Thiamethoxam toxicity in honeybees is not enhanced by common fungicide and herbicide and lacks stress-induced changes in mRNA splicing

Securing food supply for a growing population is one of the current major challenges and heavily relies on the use of agrochemicals to maximize crop yield. Neonicotinoids are globally one of the most widely used insecticides. It is increasingly recognized, that neonicotinoids have a negative impact on non-target organisms, including important pollinators such as the European honey bee Apis mellifera. Toxicity of neonicotinoids may be enhanced through simultaneous exposure with additional pesticides, which could help explain, in part, the global decline of honey bee colonies. Here we examined whether exposure effects of the neonicotinoid Thiamethoxam are enhanced by the commonly used fungicide Carbendazim and the herbicide Glyphosate. For the first time, we also analysed alternative splicing changes upon pesticide exposure in the honey bee. In particular, we examined transcripts of three genes: i) the stress sensor gene X box binding protein-1 (Xbp1), ii) the Down Syndrome Cell Adhesion Molecule (Dscam) gene and iii) the embryonic lethal/abnormal visual system (elav) gene, both important genes for neuronal function. Our results indicate that neonicotinoid toxicity applied at sub-lethal doses is not enhanced by Carbendazim nor Glyphosate. Likewise, toxicity of these compounds did not impact on the complex process of spliceosomal-directed joining of exons and non-spliceosomal intron excision in the analysed mRNAs.