{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:42:51Z","timestamp":1788172971560,"version":"build-2803163510"},"reference-count":60,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T00:00:00Z","timestamp":1686441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The insecticides spinosad and imidacloprid are neurotoxins with distinct modes of action. Both target nicotinic acetylcholine receptors (nAChRs), albeit different subunits. Spinosad is an allosteric modulator, that upon binding initiates endocytosis of its target, nAChR\u03b16. Imidacloprid binding triggers excessive neuronal ion influx. Despite these differences, low\u2010dose effects converge downstream in the precipitation of oxidative stress and neurodegeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Using RNA\u2010sequencing, we compared the transcriptional signatures of spinosad and imidacloprid, at low\u2010dose exposures. Both insecticides cause up\u2010regulation of glutathione S\u2010transferase and cytochrome P450 genes in the brain and down\u2010regulation in the fat body, whereas reduced expression of immune\u2010related genes is observed in both tissues. Spinosad shows unique impacts on genes involved in lysosomal function, protein folding, and reproduction. Co\u2010expression analyses revealed little to no correlation between genes affected by spinosad and <jats:italic>nAChR\u03b16<\/jats:italic> expressing neurons, but a positive correlation with glial cell markers. We also detected and experimentally confirmed <jats:italic>nAChR\u03b16<\/jats:italic> expression in fat body cells and male germline cells. This led us to uncover lysosomal dysfunction in the fat body following spinosad exposure, and a fitness cost in spinosad\u2010resistant (<jats:italic>nAChR\u03b16<\/jats:italic> null) males \u2013 oxidative stress in testes, and reduced fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Spinosad and imidacloprid share transcriptional perturbations in immunity\u2010, energy homeostasis\u2010, and oxidative stress\u2010related genes. Low doses of other neurotoxic insecticides should be investigated for similar impacts. While target\u2010site spinosad resistance mutation has evolved in the field, this may have a fitness cost. Our findings demonstrate the power of tissue\u2010specific transcriptomics approach and the use of single\u2010cell transcriptome data. \u00a9 2023 The Authors. <jats:italic>Pest Management Science<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ps.7585","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T22:58:59Z","timestamp":1685401139000},"page":"3913-3925","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Tissue\u2010specific transcriptome analyses in <i>Drosophila<\/i> provide novel insights into the mode of action of the insecticide spinosad and the function of its target, <scp><i>nAChR\u03b16<\/i><\/scp>"],"prefix":"10.1002","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4783-9025","authenticated-orcid":false,"given":"Felipe","family":"Martelli","sequence":"first","affiliation":[{"name":"School of BioSciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3321-2619","authenticated-orcid":false,"given":"Thomas A.","family":"Ravenscroft","sequence":"additional","affiliation":[{"name":"Janelia Research Campus Howard Hughes Medical Institute  Ashburn VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hutchison","sequence":"additional","affiliation":[{"name":"School of BioSciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9840-9119","authenticated-orcid":false,"given":"Philip","family":"Batterham","sequence":"additional","affiliation":[{"name":"School of BioSciences The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2014.04.009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2014.12.041"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2019.09.006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2009.11.008"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax9931"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2011828117"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73812"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1910(87)90025-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2003667117"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2007.12.007"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010522"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2015.01.017"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2006.11.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.6290"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0142-20.2020"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk2432"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.057"},{"key":"e_1_2_7_19_1","volume-title":"In Vivo Functional Characterization of Nicotinic Acetylcholine Receptors in Drosophila Melanogaster","author":"Luong HNB","year":"2018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-4-r36"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4599"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.4498"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.23"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.03.011"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-112408-085356"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-ento-011118-112007"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.09.020"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ento.44.1.507"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812141106"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1534\/g3.114.013870"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2583.2004.00529.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3570065"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.02.033"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-021-09990-7"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2021.103547"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09800-2"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.019"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.08.024"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020552"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-6480(69)90222-6"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20229"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.07.027"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M000646"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034745"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2017.69"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.15503"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibmb.2012.07.010"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.5689"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2016.02.006"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12029"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000802"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jes.2015.12.027"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.baae.2018.05.001"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327110388959"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2010.07.006"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2016.05.003"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.04.006"}],"container-title":["Pest Management Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ps.7585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:29:50Z","timestamp":1761053390000},"score":1,"resource":{"primary":{"URL":"https:\/\/scijournals.onlinelibrary.wiley.com\/doi\/10.1002\/ps.7585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,11]]},"references-count":60,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/ps.7585"],"URL":"https:\/\/doi.org\/10.1002\/ps.7585","archive":["Portico"],"relation":{},"ISSN":["1526-498X","1526-4998"],"issn-type":[{"value":"1526-498X","type":"print"},{"value":"1526-4998","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,11]]},"assertion":[{"value":"2023-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}