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.

项目概要/摘要 严重疟疾会引起循环血液中生物胺组胺和血清素水平的变化 （5-羟色胺，5-HT），这些变化与人类疾病病理有关。组胺和 5-HT 也是昆虫（包括蚊子）的重要神经调节剂。我们的总体假设是 通过喂养蚊子而摄入血液中的组胺和 5-HT 通过按蚊生物胺发出信号 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 成功扩大了疟疾寄生虫的传播。这些研究的创新之处在于它们将新颖的 从蚊子生物学到疟疾的临床观察，他们重点关注蚊子摄入生物胺 血液中检测到的生理水平，它们将定义以前未探索过的按蚊肠脑轴 组胺能和血清素能信号传导。我们将通过三个具体目标来解决我们的总体假设。 在目标 1 中，我们将定义并模拟单独摄入组胺和 5-HT 以及联合摄入组胺和 5-HT 的影响范围。 组合的浓度反映了疟疾相关的和健康的血液水平。斯蒂芬西 成功感染恶性疟原虫和小鼠寄生虫约氏疟原虫 yoelii 17XNL。 我们还将研究这些治疗对服用第二次血粉倾向的影响， 耐热性、繁殖力、窝大小和寿命。在目标 2 中，我们将使用触角和视网膜记录， 行为生物测定，以确定摄入的组胺和 5-HT（单独或组合）对视觉的影响 和 An 中的嗅觉生理学。斯蒂芬西。在目标 3 中，我们将量化 An 中的内源性组胺和 5-HT。 斯蒂芬西并绘制了相关的组胺能和血清素能肠-脑信号网络。我们也会 识别和模拟摄入的生物胺对内源生物胺水平的影响和使用 组胺和 5-HT 受体拮抗剂可中断疟疾寄生虫感染的信号控制，倾向于 进行第二次血粉并在 An 中繁殖。斯蒂芬西。完成这些研究后，我们将建立 与严重疟疾相关并通过喂食蚊子摄入的生物胺浓度可以 改变蚊子的生理和生物学模式，预计有利于寄生虫传播。这样的 未来可以利用这些知识将传播控制与临床干预措施联系起来（例如，减少 组胺升高并逆转 5-HT 下降，以减轻人类疟疾疾病）以及未来 开发新型诱饵来操纵媒介蚊子中的生物胺信号传导。