Endothelial monoamine neurotransmitter metabolism at the blood-brain barrier
血脑屏障内皮单胺神经递质代谢
基本信息
- 批准号:10586780
- 负责人:
- 金额:$ 39.5万
- 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:2022-09-20 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAmino AcidsAmygdaloid structureAnxietyBehaviorBloodBlood - brain barrier anatomyBlood VesselsBrainBrain regionCellsChromosome MappingCommunitiesCuesDOPA decarboxylaseDataDopamineDopamine AgonistsDopamine AntagonistsEndothelial CellsEndotheliumEnzymesEpilepsyFunctional disorderGenesGeneticGenetic TranscriptionGlucoseHaloperidolHealthHigh Pressure Liquid ChromatographyHormonesHousingImmunologic SurveillanceIonsKnock-outKnockout MiceLateralLeadLearningLightLinkMeasuresMetabolicMetabolic PathwayMetabolismModelingModificationMonoamine OxidaseMoodsMovementMultiple SclerosisMusNeuraxisNeurodevelopmental DisorderNeuromodulatorNeuronsNeurophysiology - biologic functionNeurotransmittersNutrientPain DisorderParkinson DiseasePhenotypeProcessPropertyProteinsRegulationRewardsSerotoninSignal TransductionSignaling MoleculeSocial BehaviorSocial InteractionSocial isolationStimulusStrokeSynapsesSystemTestingTight JunctionsTissuesToxinTranslationsVascular Endothelial Cellapproach behaviorbehavioral responseblood-brain barrier functionbrain endothelial cellbrain tissueexperienceextracellularhabituationliquid chromatography mass spectrometrymonoaminemouse modelnervous system disorderneural circuitneuropsychiatric disorderneurotransmitter metabolismnovelpainful neuropathypathogenrelating to nervous systemresponseropinirolesensory stimulussocialspatial memorysynaptic functiontranscytosisuptake
项目摘要
The term blood-brain barrier collectively describes the properties of central nervous system (CNS) vasculature
which stringently regulate the movement of ions, molecules and cells between the blood and neural tissue. These
properties protect the CNS from toxins, pathogens and CNS immune surveillance, and provide the neural tissue
the necessary nutrients for proper function. The vascular endothelial cells of the CNS confer many of the
properties of the blood-brain barrier, they form paracellular and transcellular barriers, and possess distinct
transport properties that efflux potential toxins and deliver nutrients. Blood-brain barrier dysfunction is observed
in a wide array of neurological diseases including epilepsy, multiple sclerosis, stroke, Parkinson’s Disease and
Alzheimer’s Disease. The objective of this study is to identify novel genes that allow the blood-brain barrier to
regulate the health and function of the CNS. We identified several genes highly enriched in CNS endothelial cells
which are involved in the synthesis and degradation of monoamine neurotransmitters, dopamine and serotonin.
Dopamine and serotonin are neuromodulators as they potentiate the firing rate of neurons. Outside of the
synapse they function as traditional extracellular signaling molecules and hormones. Neural circuits incorporating
dopamine and serotonin are involved in learning, reward, movement and mood, while dysfunction in
monoaminergic systems are observed in a host of neurological diseases including Parkinson’s Disease,
Alzheimer’s Disease, neuropathic pain and neuropsychiatric disorders. Metabolism of dopamine and serotonin
by brain endothelial cells could be involved in the many processes and behaviors regulated by these monoamine
neurotransmitters. To determine the functions of blood-brain barrier monoamine neurotransmitter metabolism,
we generated conditional endothelial-specific knockouts of Ddc, MaoA and MaoB and examined the requirement
of these genes in behavior and the brain levels of dopamine and serotonin. Our preliminary studies suggest that
blood-brain barrier monoamine metabolism regulates the levels of monoamines in a behavior context-dependent
manner. We will use the conditional endothelial-specific knockout mouse models to examine how the blood-brain
barrier regulates behavior responses to sensory stimuli and determine the mechanisms by which blood-brain
barrier monoamine metabolism regulates monoamine neurotransmitter levels and behavior. Lastly, we will
examine if brain monoamine signaling is altered in endothelial-specific knockouts of blood-brain barrier
monoamine metabolic genes.
血脑屏障这一术语统称为描述了中枢神经系统(CNS)和血管系统的重要特性。
它严格地调节血液中的离子、分子和细胞在血液和神经组织之间的运动。
保护中枢神经系统免受毒素、病原体和免疫系统监视的特性,以及为中枢神经系统提供免疫系统组织的特性。
正常的神经功能需要必要的营养。中枢神经系统的血管内皮细胞和血管内皮细胞提供了许多功能。
血脑屏障的性质可以形成跨细胞屏障和跨细胞屏障,它们具有截然不同的特点。
运输特性表明,血液流出的是潜在的毒素,并提供营养物质。血脑屏障和功能障碍是观察到的。
在中国,一系列常见的神经系统疾病,包括癫痫、多发性硬化症、中风、帕金森氏症等。
阿尔茨海默氏病。这项研究的主要目标是进一步确定新的遗传基因,使人类的血脑屏障功能得以发挥作用。
调节中枢神经系统的健康和功能。我们已经确定了几个在中枢神经系统内皮细胞中高度富含蛋白质的易感基因。
它们也参与了单胺类神经递质、多巴胺和5-羟色胺的合成和降解过程。
多巴胺和5-羟色胺是两种神经调节剂,因为它们可以增强神经元的放电频率。
突触说,它们的功能类似于传统的细胞外信号转导分子和荷尔蒙。神经回路正在整合细胞外信号。
多巴胺和5-羟色胺参与学习、奖赏、运动和情绪,而大脑功能障碍则与此有关。
在包括帕金森氏症在内的多种神经系统疾病的宿主中,也观察到了单胺类神经系统。
阿尔茨海默氏症、神经病理性疼痛和神经精神性精神障碍,以及多巴胺和5-羟色胺代谢障碍。
通过大脑,内皮细胞可能也参与了许多神经过程和行为的调节,这些神经单胺类物质。
神经递质。旨在确定血脑屏障和单胺类神经递质的主要功能。
我们生成了DDC、MAOA和MAOB的有条件的内皮特异性基因敲除规则,并根据规则要求进行了审查。
在这些基因中,有一些与行为有关,并影响了大脑中多巴胺和血清素的水平。我们的初步研究表明,这一点是正确的。
血脑屏障和单胺类物质的代谢在一定程度上调节着单胺类物质的水平,这是一种与上下文相关的行为。
方式。我们将不会使用新的有条件的内皮特异性基因敲除小鼠模型来进一步研究血液脑是如何变化的。
屏障蛋白调节人的行为和对感官刺激的反应,并决定影响血液和大脑的免疫机制。
单胺类神经代谢屏障调节单胺类神经递质水平和行为。最后,我们将继续努力。
检查在血脑屏障的内皮特异性基因敲除过程中,大脑中的单胺类信号通路是否发生了变化。
单胺与新陈代谢相关基因。
项目成果
期刊论文数量(0)
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Roeben Munji其他文献
Roeben Munji的其他文献
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{{ truncateString('Roeben Munji', 18)}}的其他基金
Endothelial monoamine neurotransmitter metabolism at the blood-brain barrier
血脑屏障内皮单胺神经递质代谢
- 批准号:
10707495 - 财政年份:2022
- 资助金额:
$ 39.5万 - 项目类别:
Regulation of spinal cord development and the Wnt signaling pathway by Oto
Oto 调控脊髓发育和 Wnt 信号通路
- 批准号:
7485692 - 财政年份:2007
- 资助金额:
$ 39.5万 - 项目类别:
Regulation of spinal cord development and the Wnt signaling pathway by Oto
Oto 调控脊髓发育和 Wnt 信号通路
- 批准号:
7678362 - 财政年份:2007
- 资助金额:
$ 39.5万 - 项目类别:
Regulation of spinal cord development and the Wnt signaling pathway by Oto
Oto 调控脊髓发育和 Wnt 信号通路
- 批准号:
7328890 - 财政年份:2007
- 资助金额:
$ 39.5万 - 项目类别: