Data repository for the publication "Functional expression of nicotinic receptors on iPSC-derived astrocytes and signalling disturbances by a panel of neonicoinoid pesticides and their metabolites"

This dataset provides the raw data from the publication "Functional expression of nicotinic receptors on iPSC-derived astrocytes and signalling disturbances by a panel of neonicoinoid pesticides and their metabolites", an overview of the calculated benchmark concentrations and performed statistics for each figure. Below the abstract is provided as a short description of the publication. Little is known about how nicotinic signalling in human astrocytes may contribute to the functional neurotoxicity of compounds related to tobacco alkaloids and neonicotinoid pesticides. We generated a single-cell Ca2+-imaging assay in induced pluripotent stem cells (iPSCs)-derived astrocytes, and profiled functional expressions of some neurotoxicologically relevant receptors. Responses to pharmacological tool compounds indicated the expression of nicotinic, muscarinic, purinergic, glutamatergic receptors and voltage-gated Na+/Ca2+ channels. Closer investigation of the nicotinic system, e.g. using the alpha7 nicotinic acetylcholine receptor (nAChR)-selective positive allosteric modulator PNU‑120596, an alpha7-preferring agonist (AR‑R17779), and the antagonist tubocurarine, demonstrated that Ca2+ signals elicited by nicotine and neonicotinoids are dominated by alpha7 nAChRs and depend on downstream activation of L-type Ca2+ channels and tetrodotoxin-sensitive Na+ channels. Crosstalk of nAChR activation/desensitization was neither observed for the inflammatory response elicited by TNF nor for activation of glutamatergic or purinergic signalling. However, pre-stimulation of nAChR by neonicotinoids significantly blunted the response to the neurotransmitter acetylcholine. Comparative experiments in LUHMES neurons revealed similar potency ranges and pharmacological fingerprints for several neonicotinoids and their human-relevant metabolites descyanothiacloprid and desnitroimidacloprid, with the tested metabolites being more potent than their parent pesticides. After the basic system characterization, the data-poor pesticides cycloxaprid and flupyradifurone were profiled in the astrocyte and LUHMES neuron test systems. They showed the typical features of alpha7 nAChR agonists. The observed disruption of cholinergic signalling suggests that neonicotinoids may impair astrocyte–neuron communication in human brains. This study implements human iPSC-derived astrocytes as a mechanistically anchored test system for neurotoxicity screening.