Molecular Effects of Neonicotinoids in Honey Bees (Apis mellifera)

Abstract

Neonicotinoids are implicated in the decline of bee populations. As agonists of nicotinic acetylcholine receptors, they disturb acetylcholine receptor signaling leading to neurotoxicity. Several behavioral studies showed the link between neonicotinoid exposure and adverse effects on foraging activity and reproduction. However, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic levels of three neonicotinoids and nicotine, and compared laboratory studies to field exposures with acetamiprid. We assessed transcriptional alterations of eight selected genes in caged honey bees exposed to different concentrations of the neonicotinoids acetamiprid, clothianidin, imidacloporid, and thiamethoxam, as well as nicotine. We determined transcripts of several targets, including nicotinic acetylcholine receptor α 1 and α 2 subunit, the multifunctional gene vitellogenin, immune system genes apidaecin and defensin-1, stress-related gene catalase and two genes linked to memory formation, pka and creb. Vitellogenin showed a strong increase upon neonicotinoid exposures in the laboratory and field, while creb and pka transcripts were down-regulated. The induction of vitellogenin suggests adverse effects on foraging activity, whereas creb and pka down-regulation may be implicated in decreased long-term memory formation. Transcriptional alterations occurred at environmental concentrations and provide an explanation for the molecular basis of observed adverse effects of neonicotinoids to bees.

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

“…To understand how neonicotinoids affect behavior and immunity at the molecular level, Christen et al (2016) looked at transcriptional regulation of 8 genes in caged honeybees fed with field-realistic concentrations of acetamiprid, clothianidin, imidacloprid, and thiamethoxam. They found downregulation of transcription of two genes involved in memory and increased transcription of the gene responsible for vitellogenin, the latter possibly affecting foraging behavior.…”

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 1: new molecules, metabolism, fate, and transport

“…Christen et al (2016) observed that clothianidin, imidacloprid, thiamethoxam, and acetamiprid led to expressional changes of immune system-related genes in honeybees at environmental realistic concentrations. The investigations covered the single compounds as well as their binary mixtures (Christen et al 2016).…”

Weight of evidence evaluation of a network of adverse outcome pathways linking activation of the nicotinic acetylcholine receptor in honey bees to colony death

“…Further, inhibition of nAChR activity from desensitization can lead to an up-regulation in nAChR expression, termed pharmacological chaperoning (Srinivasan et al, 2012;Flores et al, 1992;Marszalec et al, 2005). Exposure to imidacloprid and thiamethoxam for 72 or 48 h, respectively was shown to significantly increase transcriptional abundance of nAChRα1 subunit in the honey bee brain (Christen et al, 2016). In the desensitized state, nAChR receptors have high affinity for the agonist and therefore establish a blockade to subsequent agonist binding (Ochoa et al, 1989).…”

“…Closure of the receptor, due to prolonged desensitization is likely to impede Ca 2+ signaling across the nAChR and, hence, downstream components of the pathway, although studies specifically evaluating such desensitization and impacts on Ca 2+ signaling in the insect neuron are lacking. However, Christen et al (2016) evaluated PKA and CREB gene expression in the brain after oral exposure of honey bees to neonicotinoids. Protein kinase A transcripts were significantly decreased after 72 h of exposure to 3 ng imidacloprid/bee and after 48 h of exposure to 0.3 ng clothianidin/bee (Christen et al, 2016).…”

“…However, Christen et al (2016) evaluated PKA and CREB gene expression in the brain after oral exposure of honey bees to neonicotinoids. Protein kinase A transcripts were significantly decreased after 72 h of exposure to 3 ng imidacloprid/bee and after 48 h of exposure to 0.3 ng clothianidin/bee (Christen et al, 2016). Additionally CREB was significantly decreased after 48 h of exposure to 3 ng imidacloprid/bee and increased after a 24 h exposure to 0.3 ng clothianidin/bee.…”