Global transcriptomic effects of environmentally relevant concentrations of the neonicotinoids clothianidin, imidacloprid and thiamethoxam in honey bees (Apis mellifera)

Neonicotinoids are implicated in the decline of honey bees but the molecular basis underlying adverse effects are poorly known. Here we describe global transcriptomic profiles in the brain of honey bee workers exposed for 48 h to clothianidin, imidacloprid and thiamethoxam at environmentally realistic concentrations of 0.1 to 3 ng/bee (1-30 ng/mL sucrose solution) by high-throughput RNA-sequencing. All neonicotinoids led to significant alteration (mainly down-regulation) of gene expression, generally with a concentration-dependent effect. Among many others, genes related to metabolism and detoxification were differently expressed. Gene ontology (GO) enrichment analysis of biological processes revealed catabolic carbohydrate metabolism (regulation of enzyme activities such as amylase), lipid metabolism and transport mechanisms as shared terms between all neonicotinoids at high concentrations. KEGG pathway analysis indicated that at least two neonicotinoids induced change in expression of various metabolic pathways: pentose phosphate pathways, starch and sucrose metabolism and sulfur metabolism, in which glucose 1-dehydrogenase and alpha-amylase were down-regulated and 3'(2'),5'-bisphosphate nucleotidase up-regulated. RT-qPCR analysis confirmed the down-regulation of major royal jelly proteins, hbg3 and cyp9e2 found by RNA-seq. Our study highlights the comparative molecular effects of neonicotinoid exposure to bees. Further studies should link these effects with physiological outcomes.