Roles of hemocytes and bioactive lipids in the modulation of neuronal excitability and seizure behavior in Drosophila voltage-gated sodium channel mutants
血细胞和生物活性脂质在果蝇电压门控钠通道突变体神经元兴奋性和癫痫行为调节中的作用
基本信息
- 批准号:10559686
- 负责人:
- 金额:$ 19.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcidsAdultAffectBasic ScienceBehaviorBehavior ControlBehavioralBiologicalBiological ProcessBiologyBlood CellsBrainCandidate Disease GeneCellsCentral Nervous SystemCommunicationComplexDNA Sequence AlterationDevelopmentDietDietary ComponentDissociationDrosophila genusDrosophila melanogasterElectrophysiology (science)Experimental ModelsFamilyFoundationsFutureGenesGeneticGenetic Predisposition to DiseaseGenetic ScreeningGlutathione S-TransferaseGoalsHematopoieticHemocytesHyperactivityImmuneImmune responseImmune systemInnate Immune ResponseInnate Immune SystemInsectaInterdisciplinary StudyLarvaLinkLinolenic AcidsLipidsMacrophageMediatingMental disordersMolecularMorphologyNatural ImmunityNatureNervous SystemNeuroimmuneNeurologicNeuronsNeurophysiology - biologic functionOrthologous GeneOutcomePathologic ProcessesPhenotypePhysiologicalPhysiological ProcessesPhysiologyPlayPolyunsaturated Fatty AcidsProcessPropertyProstaglandinsProtocols documentationPublic HealthRecipeResearchRoleSeizuresSeveritiesSignal PathwaySignal TransductionSodiumSodium ChannelSolidSynthase Dbehavioral phenotypingclinically significantdietaryfeedingflyfood standardgenetic manipulationimmune functioninsightknock-downlipid mediatorlipidomicsmodel organismmutantnervous system disorderneurodevelopmentneuronal excitabilityneuropsychiatric disorderneuroregulationnovelnovel strategiespreventvoltage
项目摘要
PROJECT SUMMARY
Local and systemic interactions between the nervous system and immune system play important roles in
various physiological and pathological processes. The long-term goal of this project is to obtain a fundamental
understanding of how neuroimmune communications contribute to the regulation of neural development,
physiology, and behavior using an experimental model organism Drosophila melanogaster possessing the
evolutionarily conserved innate immune system. The overall objective in this application is to reveal the roles
and mechanisms of functional interactions between innate immune cells and the central nervous system in the
modulation of neuronal excitability and behavioral hyperactivity in seizure-prone fly voltage-gated sodium (Nav)
channel mutant, paraShu. The project is based on intriguing findings that: 1) paraShu adult seizure severity is
significantly suppressed by diet supplemented with -3 polyunsaturated fatty acids (PUFAs) -linolenic acid
(ALA); 2) hemocyte (macrophage-like blood cell)-specific knockdown of GstS1, a fly ortholog of mammalian
prostaglandin D synthase, mimics the effect of dietary ALA; and 3) both dietary ALA and GstS1 knockdown are
effective during development to suppress seizures in adult mutants. The central hypothesis is that the severity
of adult paraShu is modulated through neural development by the action of innate immune cells in the biological
processes involving bioactive lipid mediators. Two specific aims will be pursued to investigate the hypothesis:
1) Define the roles of hemocytes in modulation of neuronal excitability and behavioral hyperactivity in paraShu
mutants; and 2) Identify genes and signaling pathways involved in hemocyte-dependent modulation of adult
seizures. For the first aim, hemocyte functions will be genetically perturbed and the effects on neural
development, electrophysiological properties, and seizure behavior will be examined in the presence or
absence of phenotypic modifiers using freely moving or tethered behaving adult flies as well as dissociated
primary neuronal cultures prepared from mutant larval brains. For the second aim, a candidate gene approach
will be used to identify genes involved in putative lipid signaling processes, and lipidomics analysis will be
carried out to determine the changes in oxylipins, lipid mediators produced from PUFAs, in the mutants in the
presence or absence of phenotypic modifiers. The proposed multidisciplinary research is expected to reveal
the roles of hemocytes in the diet-dependent modulation of neuronal excitability and behavioral seizures in Nav
channel mutants, and provide novel genetic and molecular insights into the largely unexplored lipid signaling
pathways that play important roles in the modulation of genetically predisposed neurological phenotypes. The
project is scientifically and clinically significant because it will lead to a deeper appreciation of the plastic and
interactive nature of the nervous system controlled by the immune system, and is expected to provide valuable
insights into future strategies to prevent and treat nervous system disorders associated with aberrant immune
function.
项目总结
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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TOSHIHIRO KITAMOTO其他文献
TOSHIHIRO KITAMOTO的其他文献
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{{ truncateString('TOSHIHIRO KITAMOTO', 18)}}的其他基金
Roles of hemocytes and bioactive lipids in the modulation of neuronal excitability and seizure behavior in Drosophila voltage-gated sodium channel mutants
血细胞和生物活性脂质在果蝇电压门控钠通道突变体神经元兴奋性和癫痫行为调节中的作用
- 批准号:
10433305 - 财政年份:2022
- 资助金额:
$ 19.31万 - 项目类别:
Effects of dietary alpha-linolenic acid on SUDEP, seizures, and neural structure and function in mouse models of epilepsy
膳食α-亚麻酸对癫痫小鼠模型中的 SUDEP、癫痫发作以及神经结构和功能的影响
- 批准号:
10527609 - 财政年份:2022
- 资助金额:
$ 19.31万 - 项目类别:
A novel GPCR-mediated steroid signaling that controls alcohol-induced behavior
一种新型 GPCR 介导的类固醇信号传导,可控制酒精诱发的行为
- 批准号:
8427822 - 财政年份:2012
- 资助金额:
$ 19.31万 - 项目类别:
A novel GPCR-mediated steroid signaling that controls alcohol-induced behavior
一种新型 GPCR 介导的类固醇信号传导,可控制酒精诱发的行为
- 批准号:
8589533 - 财政年份:2012
- 资助金额:
$ 19.31万 - 项目类别:
Studies of genes involved in the lithium responsive neurological processes
参与锂反应神经过程的基因研究
- 批准号:
7886481 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Studies of genes involved in the lithium responsive neurological processes
参与锂反应神经过程的基因研究
- 批准号:
8062045 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Studies of genes involved in the lithium responsive neurological processes
参与锂反应神经过程的基因研究
- 批准号:
8258310 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Studies of genes involved in the lithium responsive neurological processes
参与锂反应神经过程的基因研究
- 批准号:
8420519 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Studies of genes involved in the lithium responsive neurological processes
参与锂反应神经过程的基因研究
- 批准号:
7727645 - 财政年份:2009
- 资助金额:
$ 19.31万 - 项目类别:
Significance of microRNA-mediated gene regulation in chronic neuropathic pain
microRNA介导的基因调控在慢性神经病理性疼痛中的意义
- 批准号:
7617052 - 财政年份:2008
- 资助金额:
$ 19.31万 - 项目类别:
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