Biogenic amines, malaria and manipulation of mosquito physiology and behavior.

生物胺、疟疾以及蚊子生理和行为的控制。

• 批准号: 10679076
• 负责人: Shirley Luckhart
• 金额: $ 54.45万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679076
• 关键词: Abdomen; Aedes; Anopheles Genus; Behavior; Behavioral; Biogenic Amine Receptors; Biogenic Amines; Biological Assay; Biology; Bite; Blood; Body Size; Brain; Brain region; Cerebral Malaria; Clinical; Clutch Size; Collaborations; Coma; Culicidae; Dangerousness; Data; Development; Disease; Disease Progression; Enzymes; Falciparum Malaria; Feeding behaviors; Fertility; Future; Genes; Goals; Head; Histamine; Histamine Receptor; Histamine Release; Human; Hyperphenylalaninaemias; Infection; Ingestion; Insecta; Interruption; Intervention; Investments; Knowledge; Liver diseases; Longevity; Malaria; Maps; Mediating; Metabolism; Midgut; Modeling; Mus; Neuromodulator; Neurons; Parasite Control; Parasites; Parasitic infection; Pathology; Pattern; Pharmacotherapy; Physiological; Physiology; Plasma; Plasmodium berghei; Plasmodium falciparum; Plasmodium yoelii; Population; Publishing; Reporting; Reproduction; Resistance; Retina; Risk; Sensory; Serotonin; Severities; Signal Transduction; Sporozoites; Symptoms; Transcript; Tryptophan; Tyrosine; Vectorial capacity; Visual; antagonist; behavior influence; feeding; human disease; improved; innovation; insulin-like peptide; life history; mathematical model; mosquito-borne; neurophysiology; neurotransmission; novel; olfactory stimulus; receptor; receptor expression; reproductive; response; serotonin receptor; small molecule; success; trait; transmission process; treatment effect; vector mosquito; vector transmission; visual stimulus

Project Summary/Abstract Severe malaria induces changes in circulating blood levels of the biogenic amines histamine and serotonin (5-hydroxytryptamine, 5-HT) and these changes are associated with human disease pathology. Histamine and 5-HT are also important neuromodulators in insects, including mosquitoes. Our overarching hypothesis is that histamine and 5-HT, ingested in blood by feeding mosquitoes, signal through anopheline biogenic amine receptors and alter endogenous biogenic amine levels, life history traits, behavior and mosquito infection success to amplify malaria parasite transmission. These studies are innovative in that they connect novel mosquito biology to clinical observations in malaria, they focus on mosquito ingestion of biogenic amines at physiological levels detected in blood and they will define previously unexplored anopheline gut-brain axes for histaminergic and serotonergic signaling. We will address our overarching hypothesis with three Specific Aims. In Aim 1, we will define and model the scope of effects of ingested histamine and 5-HT, alone and in combination at concentrations that reflect malaria-associated and healthy blood levels, on An. stephensi infection success with Plasmodium falciparum and with the mouse parasite Plasmodium yoelii yoelii 17XNL. We will also examine the effects of these treatments on the tendency to take a second bloodmeal, thermotolerance, fecundity, clutch size and lifespan. In Aim 2, we will use antennal and retinal recordings and behavioral bioassays to define the effects of ingested histamine and 5-HT, alone and in combination, on visual and olfactory physiology in An. stephensi. In Aim 3, we will quantify endogenous histamine and 5-HT in An. stephensi and map associated histaminergic and serotonergic gut-to-brain signaling networks. We will also identify and model effects of ingested biogenic amines on levels of endogenous biogenic amines and use histamine and 5-HT receptor antagonists to interrupt signaling control of malaria parasite infection, tendency to take a second bloodmeal and reproduction in An. stephensi. With completion of these studies, we will establish that biogenic amine concentrations associated with severe malaria and ingested by feeding mosquitoes can alter mosquito physiology and biology in patterns that would be predicted to favor parasite transmission. Such knowledge can be used in the future to connect transmission control to clinical interventions (e.g., to reduce elevated histamine and reverse declines in 5-HT to mitigate human malarial disease) and for future development of novel lures to manipulate biogenic amine signaling in vector mosquitoes.

项目摘要/摘要 严重的疟疾诱导生物胺组胺和5-羟色胺的循环血液水平的变化 （5-羟化胺，5-HT），这些变化与人类疾病病理有关。组胺和 5-HT也是包括蚊子在内的昆虫中的重要神经调节剂。我们的总体假设是 通过喂食蚊子在血液中摄入的组胺和5-HT，通过瞬间生物胺发出信号 受体并改变内源性生物胺水平，生活史特征，行为和蚊子感染 成功扩大疟疾寄生虫传播的成功。这些研究具有创新性，因为它们连接了小说 蚊子生物学对疟疾的临床观察，他们专注于摄入生物胺的蚊子 在血液中检测到的生理水平，它们将定义以前未开发的态肠肠轴 组胺能和血清素能信号传导。我们将以三个具体目标来解决我们的总体假设。 在AIM 1中，我们将定义和建模单独和5-HT的摄入的组胺和5-HT的影响范围 浓度以反映疟疾相关和健康的血液水平的组合。斯蒂芬西 恶性疟原虫和小鼠寄生虫疟原虫yoelii yoelii 17xnl的感染成功。 我们还将研究这些治疗对第二次血液的趋势的影响， 温耐剂，繁殖力，离合器尺寸和寿命。在AIM 2中，我们将使用触角和视网膜记录， 行为生物测定以定义摄入的组胺和5-HT的影响，单独和组合对视觉 和嗅觉生理学斯蒂芬西。在AIM 3中，我们将在An中量化内源性组胺和5-HT。 Stephensi和MAP相关的组胺能和血清素能肠道信号网络。我们也会 识别摄入的生物胺对内源性生物胺含量的影响并模型 组胺和5-HT受体拮抗剂中断疟原虫感染的信号控制，趋势 进行第二个血液并繁殖。斯蒂芬西。通过完成这些研究，我们将建立 与严重疟疾相关的生物胺浓度并因摄取蚊子而摄入的生物胺浓度可以 在模式中改变蚊子生理和生物学，预计有利于寄生虫传播。这样的 将来可以使用知识将传输控制连接到临床干预措施（例如，减少 升高组胺和反向下降5-HT以减轻人类疟疾疾病），以后 开发新型诱饵，以操纵载体蚊子中的生物胺信号传导。