Abstract

Acetylcholine (ACh) is the major excitatory neurotransmitter in the insect central nervous system (CNS). However, besides the neuronal expression of ACh receptors (AChR), the existence of non-neuronal AChR in honeybees is plausible. The cholinergic system is a popular target of insecticides because the pharmacology of insect nicotinic acetylcholine receptors (nAChRs) differs substantially from their vertebrate counterparts. Neonicotinoids are agonists of the nAChR and are largely used in crop protection. In contrast to their relatively high safety for humans and livestock, neonicotinoids pose a threat to pollinating insects such as bees. In addition to its effects on behavior, it becomes increasingly evident that neonicotinoids affect developmental processes in bees that appear to be independent of neuronal AChRs. Brood food (royal jelly, worker jelly, or drone jelly) produced in the hypopharyngeal glands of nurse bees contains millimolar concentrations of ACh, which is required for proper larval development. Neonicotinoids reduce the secreted ACh-content in brood food, reduce hypopharyngeal gland size, and lead to developmental impairments within the colony. We assume that potential hazards of neonicotinoids on pollinating bees occur neuronally causing behavioral impairments on adult individuals, and non-neuronally causing developmental disturbances as well as destroying gland functioning.

Highlights

  • Acetylcholine (ACh) is an evolutionary highly-conserved signaling molecule

  • Imidacloprid is a partial agonist of the honeybee nicotinic acetylcholine receptors (nAChRs) (Kenyon cells: [23,33,34]; antennal lobe neurons: [22,32,62]), and clothianidin acts as a full agonist [34]

  • Several gene expression studies report an upregulation of detoxification enzymes, such as cytochrome p450s, and effects on protein translation involved in metabolic pathways after insecticide treatment [99,109,110,111,112]

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Summary

Introduction

Acetylcholine (ACh) is an evolutionary highly-conserved signaling molecule. It preceded the appearance of the nervous system since it is expressed in bacteria, archaea, in eucaryotic unicellular organisms, and in higher organisms such as plants, fungi, and animals [1]. Insect nAChRs are pentameric ionotropic receptors and cation channels with a high Ca2+ permeability (e.g., [15,16]) Their physiologies are in accordance with a function during excitatory synaptic transmission within the insect brain. Their molecular and functional similarities (e.g., high Ca2+ -permeability and sequence homologies) to the vertebrate neuronal nAChRs imply that they mediate modulatory functions. Acting via neuronal nAChRs is one of the major routes In addition to this mechanism, neonicotinoids may affect muscarinic AChRs that are, as yet, largely uncharacterized in bees. A third way, which we assume to be important for developmental effects, is via non-neuronal AChRs. Here, we review the properties of honeybee nAChRs and the actions of neonicotinoids on the neuronal receptors. We will discuss the effects of neonicotinoids on larval and adult development and present an integrative model of cholinergic signaling and disturbances by neonicotinoids

Acetylcholine Receptors in the Honeybee
Acetylcholine in Bee Development
Neonicotinoids Affect Larval and Adult Development
How Do Neonicotinoids Affect Honeybee Development?
Conclusions and Outlook
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