{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T17:38:13Z","timestamp":1775929093028,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI131609 FA9550-20-1-0422 AI148300"],"award-info":[{"award-number":["R01 AI131609 FA9550-20-1-0422 AI148300"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Approximately 3.4 billion people are at risk of malaria, a disease caused by infection with <jats:italic>Plasmodium<\/jats:italic> spp. parasites, which are transmitted by <jats:italic>Anopheles<\/jats:italic> mosquitoes. Individuals with severe falciparum malaria often exhibit changes in circulating blood levels of biogenic amines, including reduced serotonin or 5-hydroxytryptamine (5-HT), and these changes are associated with disease pathology. In insects, 5-HT functions as an important neurotransmitter for many behaviors and biological functions. In <jats:italic>Anopheles stephensi<\/jats:italic>, we show that 5-HT is localized to innervation in the head, thorax, and midgut, suggesting a gut-to-brain signaling axis that could support the effects of ingested 5-HT on mosquito biology and behavioral responses. Given the changes in blood levels of 5-HT associated with severe malaria and the key roles that 5-HT plays in insect neurophysiology, we investigated the impact of ingesting blood with healthy levels of 5-HT (1.5\u00a0\u00b5M) or malaria-associated levels of 5-HT (0.15\u00a0\u00b5M) on various aspects of <jats:italic>A. stephensi<\/jats:italic> biology. In these studies, we provisioned 5-HT and monitored fecundity, lifespan, flight behavior, and blood feeding of <jats:italic>A. stephensi.<\/jats:italic> We also assessed the impact of 5-HT ingestion on infection of <jats:italic>A. stephensi<\/jats:italic> with the mouse malaria parasite <jats:italic>Plasmodium yoelii yoelii<\/jats:italic> 17XNL and the human malaria parasite <jats:italic>Plasmodium falciparum<\/jats:italic>. Our data show that ingestion of 5-HT associated with severe malaria increased mosquito flight velocity and investigation of visual objects in response to host odor (CO<jats:sub>2<\/jats:sub>). 5-HT ingestion in blood at levels associated with severe malaria also increased the tendency to take a second blood meal 4\u00a0days later in uninfected <jats:italic>A. stephensi<\/jats:italic>. In mosquitoes infected with <jats:italic>P. y. yoelii<\/jats:italic> 17XNL, feeding tendency was decreased when midgut oocysts were present but increased when sporozoites were present. In addition to these effects, treatment of <jats:italic>A. stephensi<\/jats:italic> with 5-HT associated with severe malaria increased infection success with <jats:italic>P. y. yoelii<\/jats:italic> 17XNL compared to control, while treatment with healthy levels of 5-HT decreased infection success with <jats:italic>P. falciparum.<\/jats:italic> These changes in mosquito behavior and infection success could be used as a basis to manipulate 5-HT signaling in vector mosquitoes for improved control of malaria parasite transmission.<\/jats:p>","DOI":"10.3389\/fphys.2022.911097","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T04:33:06Z","timestamp":1654576386000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Anopheles stephensi Feeding, Flight Behavior, and Infection With Malaria Parasites are Altered by Ingestion of Serotonin"],"prefix":"10.3389","volume":"13","author":[{"given":"Anna M.","family":"Briggs","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malayna G.","family":"Hambly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel M.","family":"Sim\u00e3o-Gurge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah M.","family":"Garrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zainab","family":"Khaku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Van Susteren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin E.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A.","family":"Riffell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Luckhart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41467-022-28195-x","article-title":"The Olfactory Gating of Visual Preferences to Human Skin and Colors in Mosquitoes","volume":"13","author":"Alonso San Alberto","year":"2022","journal-title":"Nat. Commun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1177\/000456328702400613","article-title":"Blood Serotonin Levels in Adults, Autistic and Non-autistic Children-With a Comparison of Different Methodologies","volume":"24","author":"Badcock","year":"1987","journal-title":"Ann. Clin. Biochem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00441-010-0932-5","article-title":"Localization of Serotonin\/Tryptophan-Hydroxylase-Immunoreactive Cells in the Brain and Suboesophageal Ganglion of Drosophila melanogaster","volume":"340","author":"Bao","year":"2010","journal-title":"Cell Tissue Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e42821","DOI":"10.1371\/journal.pone.0042821","article-title":"Mosquito Feeding Assays to Determine the Infectiousness of Naturally Infected Plasmodium Falciparum Gametocyte Carriers","volume":"7","author":"Bousema","year":"2012","journal-title":"PLoS ONE"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fncir.2016.00005","article-title":"A Flight Sensory-Motor to Olfactory Processing Circuit in the Moth Manduca Sexta","volume":"10","author":"Bradley","year":"2016","journal-title":"Front. Neural Circuits"},{"key":"B6","doi-asserted-by":"publisher","first-page":"591","DOI":"10.3390\/nu10050591","article-title":"Dietary Neurotransmitters: A Narrative Review on Current Knowledge","volume":"10","author":"Briguglio","year":"2018","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","first-page":"20170339","DOI":"10.1098\/rspb.2017.0339","article-title":"Co-Option of a Motor-To-Sensory Histaminergic Circuit Correlates with Insect Flight Biomechanics","volume":"284","author":"Chapman","year":"2017","journal-title":"Proc. R. Soc. B"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5588","DOI":"10.1073\/pnas.1722379115","article-title":"Flight Motor Networks Modulate Primary Olfactory Processing in the Moth Manduca Sexta","volume":"115","author":"Chapman","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1111\/jam.15012","article-title":"Microbial Production of Beneficial Indoleamines (Serotonin and Melatonin) with Potential Application to Biotechnological Products for Human Health","volume":"131","author":"Danilovich","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"284","DOI":"10.4269\/ajtmh.2000.62.284","article-title":"Cerebrospinal Fluid Studies in Children with Cerebral Malaria: An Excitotoxic Mechanism?","volume":"62","author":"Dobbie","year":"2000","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B11","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1093\/qjmed\/92.9.495","article-title":"Hyperphenylalaninaemia in Children with Falciparum Malaria","volume":"92","author":"Enwonwu","year":"1999","journal-title":"Qjm"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jinsphys.2011.08.015","article-title":"Serotonin Depresses Feeding Behaviour in Ants","volume":"58","author":"Falibene","year":"2012","journal-title":"J. Insect Physiology"},{"key":"B13","volume-title":"World Malaria Report 2020: 20 Years of Global Progress and Challenges","year":"2020"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1126\/science.6805073","article-title":"Serotonin and Octopamine in the Nematode Caenorhabditis elegans","volume":"216","author":"Horvitz","year":"1982","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","first-page":"4218","DOI":"10.1016\/j.cub.2019.10.042","article-title":"Serotonergic Modulation of Walking in Drosophila","volume":"29","author":"Howard","year":"2019","journal-title":"Curr. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0181865","DOI":"10.1371\/journal.pone.0181865","article-title":"Anatomy and Behavioral Function of Serotonin Receptors in Drosophila melanogaster Larvae","volume":"12","author":"Huser","year":"2017","journal-title":"PLoS ONE"},{"key":"B17","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.neuroscience.2011.06.058","article-title":"Serotonin Receptor Activity Is Necessary for Olfactory Learning and Memory in Drosophila melanogaster","volume":"192","author":"Johnson","year":"2011","journal-title":"Neuroscience"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e00136","DOI":"10.1128\/mSphere.00136-21","article-title":"Additional Feeding Reveals Differences in Immune Recognition and Growth of Plasmodium Parasites in the Mosquito Host","volume":"6","author":"Kwon","year":"2021","journal-title":"mSphere"},{"key":"B19","doi-asserted-by":"publisher","first-page":"E9822","DOI":"10.1073\/pnas.1808243115","article-title":"Serotonin Signaling Regulates Insulin-like Peptides for Growth, Reproduction, and Metabolism in the Disease Vector Aedes aegypti","volume":"115","author":"Ling","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1111\/j.1471-4159.1974.tb06928.x","article-title":"Serotonin Deficiency in Experimental Hyperphenylalaninemia","volume":"23","author":"Loo","year":"1974","journal-title":"J. Neurochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1128\/IAI.02106-05","article-title":"Elevated Plasma Phenylalanine in Severe Malaria and Implications for Pathophysiology of Neurological Complications","volume":"74","author":"Lopansri","year":"2006","journal-title":"Infect. Immun."},{"key":"B22","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.coi.2015.07.002","article-title":"Host-Pathogen Interactions in Malaria: Cross-Kingdom Signaling and Mitochondrial Regulation","volume":"36","author":"Luckhart","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/B978-0-12-805350-8.00002-7","article-title":"Conservation and Convergence of Immune Signaling Pathways with Mitochondrial Regulation in Vector Arthropod Physiology","volume":"1","author":"Luckhart","year":"2017","journal-title":"Arthropod Vector Control. Dis. Transm."},{"key":"B24","doi-asserted-by":"publisher","first-page":"20201093","DOI":"10.1098\/rspb.2020.1093","article-title":"Age Influences the Thermal Suitability of Plasmodium Falciparum Transmission in the Asian Malaria Vector Anopheles stephensi","volume":"287","author":"Miazgowicz","year":"2020","journal-title":"Proc. R. Soc. B"},{"key":"B25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.plaphy.2018.08.031","article-title":"Novel Perspectives on the Molecular Crosstalk Mechanisms of Serotonin and Melatonin in Plants","volume":"132","author":"Mukherjee","year":"2018","journal-title":"Plant Physiology Biochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1111\/j.1474-9726.2007.00303.x","article-title":"Serotonin Receptors Antagonistically modulateCaenorhabditis Eleganslongevity","volume":"6","author":"Murakami","year":"2007","journal-title":"Aging Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.neuropharm.2011.04.003","article-title":"Possible Involvement of Serotonin 5-HT2 Receptor in the Regulation of Feeding Behavior through the Histaminergic System","volume":"61","author":"Murotani","year":"2011","journal-title":"Neuropharmacology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-38806-1","article-title":"The Pharmacological and Functional Characterization of the Serotonergic System in Anopheles gambiae and Aedes aegypti: Influences on Flight and Blood-Feeding Behavior","volume":"9","author":"Ngai","year":"2019","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.pt.2019.04.010","article-title":"Blood-Brain Barrier in Cerebral Malaria: Pathogenesis and Therapeutic Intervention","volume":"35","author":"Nishanth","year":"2019","journal-title":"Trends Parasitol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1093\/jmedent\/31.4.600","article-title":"Serotonin Depletion Affects Blood-Feeding but Not Host-Seeking Ability in Aedes triseriatus (Diptera: Culieidae)","volume":"31","author":"Novak","year":"1994","journal-title":"J. Med. Entomology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1186\/s13071-019-3513-9","article-title":"Time-of-Day of Blood-Feeding: Effects on Mosquito Life History and Malaria Transmission","volume":"12","author":"O\u2019Donnell","year":"2019","journal-title":"Parasites Vectors"},{"key":"B32","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.micinf.2013.01.003","article-title":"The Effects of Ingested Mammalian Blood Factors on Vector Arthropod Immunity and Physiology","volume":"15","author":"Pakpour","year":"2013","journal-title":"Microbes Infect."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1128\/IAI.00024-12","article-title":"Ingested Human Insulin Inhibits the Mosquito NF-\u03bab-dependent Immune Response to Plasmodium Falciparum","volume":"80","author":"Pakpour","year":"2012","journal-title":"Infect. Immun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.cois.2014.07.001","article-title":"Effects of Ingested Vertebrate-Derived Factors on Insect Immune Responses","volume":"3","author":"Pakpour","year":"2014","journal-title":"Curr. Opin. Insect Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s004420100720","article-title":"How Well Do Multivariate Data Sets Match? the Advantages of a Procrustean Superimposition Approach over the Mantel Test","volume":"129","author":"Peres-Neto","year":"2001","journal-title":"Oecologia"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.1042\/BCJ20160271","article-title":"Two Insulin-like Peptides Differentially Regulate Malaria Parasite Infection in the Mosquito through Effects on Intermediary Metabolism","volume":"473","author":"Pietri","year":"2016","journal-title":"Biochem. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e16843","DOI":"10.7554\/eLife.16843","article-title":"Serotonin Signaling Mediates Protein Valuation and Aging","volume":"5","author":"Ro","year":"2016","journal-title":"ELife"},{"key":"B38","doi-asserted-by":"publisher","first-page":"719","DOI":"10.3390\/biom11050719","article-title":"Histamine Ingestion by Anopheles stephensi Alters Important Vector Transmission Behaviors and Infection Success with Diverse Plasmodium Species","volume":"11","author":"Rodriguez","year":"2021","journal-title":"Biomolecules"},{"key":"B39","doi-asserted-by":"publisher","first-page":"40","DOI":"10.2307\/2992207","article-title":"Extensions of the Procrustes Method for the Optimal Superimposition of Landmarks","volume":"39","author":"Rohlf","year":"1990","journal-title":"Syst. Zool."},{"key":"B40","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1046\/j.1471-4159.2003.02036.x","article-title":"Co-Ordinated Expression of 5-HT2C Receptors with the NCX1 Na+\/Ca2+ Exchanger in Histaminergic Neurones","volume":"87","author":"Sergeeva","year":"2003","journal-title":"J. Neurochem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"24900","DOI":"10.1073\/pnas.2003976117","article-title":"A New Malaria Vector in Africa: Predicting the Expansion Range of Anopheles stephensi and Identifying the Urban Populations at Risk","volume":"117","author":"Sinka","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1042\/BCJ20210100","article-title":"\u03b1-Methyl-l-tryptophan as a Weight-Loss Agent in Multiple Models of Obesity in Mice","volume":"478","author":"Sivaprakasam","year":"2021","journal-title":"Biochem. J."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e0174172","DOI":"10.1371\/journal.pone.0174172","article-title":"Opposite Effects of 5-HT\/AKH and Octopamine on the Crop Contractions in Adult Drosophila melanogaster: Evidence of a Double Brain-Gut Serotonergic Circuitry","volume":"12","author":"Solari","year":"2017","journal-title":"PLoS ONE"},{"key":"B44","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/0278-5846(91)90020-2","article-title":"Alpha-Methyltryptophan as a Therapeutic Agent","volume":"15","author":"Sourkes","year":"1991","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e1007418","DOI":"10.1371\/journal.ppat.1007418","article-title":"Inhibition of JNK Signaling in the Asian Malaria Vector Anopheles stephensi Extends Mosquito Longevity and Improves Resistance to Plasmodium Falciparum Infection","volume":"14","author":"Souvannaseng","year":"2018","journal-title":"PLoS Pathog."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.cub.2020.01.018","article-title":"A Population of Interneurons Signals Changes in the Basal Concentration of Serotonin and Mediates Gain Control in the Drosophila Antennal Lobe","volume":"30","author":"Suzuki","year":"2020","journal-title":"Curr. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/35000609","article-title":"Food and Metabolic Signalling Defects in a Caenorhabditis elegans Serotonin-Synthesis Mutant","volume":"403","author":"Sze","year":"2000","journal-title":"Nature"},{"key":"B48","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/jee\/91.4.841","article-title":"The Indole Alkaloid Tryptamine Impairs Reproduction in Drosophila melanogaster","volume":"91","author":"Thomas","year":"1998","journal-title":"J. Econ. Entomology"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2740","DOI":"10.1038\/s41467-019-10805-w","article-title":"Publisher Correction: Plasmodium Falciparum Sexual Differentiation in Malaria Patients Is Associated with Host Factors and GDV1-dependent Genes","volume":"10","author":"Usui","year":"2019","journal-title":"Nat. Commun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0896-6273(00)80527-9","article-title":"Control of Alternative Behavioral States by Serotonin in Caenorhabditis elegans","volume":"21","author":"Waggoner","year":"1998","journal-title":"Neuron"},{"key":"B51","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ymgme.2017.10.009","article-title":"Tanja Scherer, Beat Th\u00f6ny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, and Cary O. HardingBlood Phenylalanine Reduction Corrects CNS Dopamine and Serotonin Deficiencies and Partially Improves Behavioral Performance in Adult Phenylketonuric Mice","volume":"123","author":"Winn","year":"2018","journal-title":"Mol. Genet. Metabolism"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e113012","DOI":"10.1371\/journal.pone.0113012","article-title":"Neuromechanism Study of Insect-Machine Interface: Flight Control by Neural Electrical Stimulation","volume":"9","author":"Zhao","year":"2014","journal-title":"PLoS ONE"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.911097\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T04:33:09Z","timestamp":1654576389000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2022.911097\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":52,"alternative-id":["10.3389\/fphys.2022.911097"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2022.911097","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,7]]},"article-number":"911097"}}