In vivo three-photon microscopy of the cortical gray and white matter
皮质灰质和白质的体内三光子显微镜
基本信息
- 批准号:10712406
- 负责人:
- 金额:$ 58.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAgeAreaAxonBehaviorBehavior TherapyBehavioralBiologyBrainBrain regionCell DeathCell Differentiation processCell LineageCell ProliferationCentral Nervous SystemCommunitiesCortical ColumnCuesDataDemyelinationsDevelopmentEnvironmentFluorescenceFutureGenerationsIndividualInflammatoryInjuryKnowledgeLearningLesionLifeMemoryMethodologyMonitorMultiple SclerosisMyelinMyelin SheathNatural regenerationNeuronsOligodendrogliaOpticsPathologicPatientsPenetrationPersonsPhotonsPhysicsRecovery of FunctionRegulationResearchShapesStructureTissue imagingTissuesUnited StatesWhite Matter Diseasecell behaviorcentral nervous system demyelinating disordercognitive functioneffectiveness evaluationefficacy testingexperiencegray matterillness lengthin vivoin vivo imaginginnovationinsightmotor learningmultiple sclerosis patientmyelinationneuronal cell bodynovelnovel therapeuticsoligodendrocyte lineageoligodendrocyte precursorprecursor cellregenerativeregional differenceremyelinationrepairedtherapeutic candidatethree photon microscopytoolwhite matterwhite matter damage
项目摘要
PROJECT SUMMARY
Multiple Sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system that afflicts
nearly 1 million people in the United States alone. While MS is classically regarded as a white matter disease,
gray matter lesion load may exceed that of the white matter in patients with MS. The pathological features of
lesions differ between gray and white matter lesions. Interestingly, in lesions that span white and gray matter
regions, display pathological hallmarks of white matter-only lesions, suggesting that cellular environments
distinctly regulate oligodendrocyte loss and regeneration. Furthermore, attempts at remyelination are more
frequent in cortical versus white matter lesions regardless of patient age or disease duration. These findings
suggest that remyelination of gray matter regions may be specifically limited by decreased functional integration
of new oligodendrocytes compared to white matter regions. Understanding the regional differences in
oligodendrocyte loss and regeneration represents a clear unmet need in the MS research community. A major
limitation to understanding these regional differences is the inability to monitor the dynamics of oligodendrocytes
in white matter in the living brain. To overcome this obstacle, we will use new optical methodologies to determine
regional variability in oligodendrocyte cell behavior. We propose to use the superior penetration depth of three-
photon excitation fluorescence and longitudinal in vivo imaging to determine the effects of circuit-specific
neuronal activity and demyelinating injury on oligodendrocyte lineage cells in both superficial and deep areas of
the adult brain. The objectives of this proposal are: 1) evaluate how behaviorally-relevant neuronal activity
regulates gray and white matter oligodendrogenesis, 2) to elucidate whether behavioral interventions can equally
promote oligodendrocyte regeneration of the gray and white matter. The overall hypothesis of this proposal is
region-specific rates of oligodendrocyte precursor differentiation and integration govern the proportion of
myelination in healthy, adaptive, and regenerative contexts. This proposal represents a novel synthesis of
cutting-edge approaches in optical physics and oligodendrocyte biology, and breaks new ground in
understanding the mechanisms underlying the regulation of gray and white matter oligodendrocyte plasticity and
regeneration.
项目摘要
多发性硬化症(MS)是一种中枢神经系统的炎性脱髓鞘疾病,
仅在美国就有近一百万人。虽然MS通常被认为是一种白色物质疾病,
在MS患者中,灰质病变负荷可能超过白色物质。
病变在灰质和白色物质病变之间不同。有趣的是,在跨越白色和灰质的病变中,
区域,显示白色病变的病理标志,表明细胞环境
明显调节少突胶质细胞的损失和再生。此外,髓鞘再生的尝试
常见于皮质与白色病变,与患者年龄或病程无关。这些发现
提示灰质区域髓鞘再生可能受到功能整合减少的特定限制
与白色区相比,新的少突胶质细胞的数量。了解区域差异,
少突胶质细胞的损失和再生代表了MS研究界中明显未满足的需求。一个主要
理解这些区域性差异的局限性是不能监测少突胶质细胞的动态
存在于活体大脑中的白色物质中。为了克服这一障碍,我们将使用新的光学方法来确定
少突胶质细胞行为的区域变异性。我们建议使用三种不同的上级穿透深度-
光子激发荧光和纵向体内成像,以确定电路特异性
神经元活性和脱髓鞘损伤对少突胶质细胞系细胞在浅表和深部的
成人大脑该建议的目标是:1)评估行为相关的神经元活动
调节灰质和白色质少突胶质细胞的发生,2)阐明行为干预是否同样可以
促进灰质和白色物质的少突胶质细胞再生。这一提议的总体假设是
少突胶质细胞前体分化和整合的区域特异性速率决定了
髓鞘形成在健康、适应性和再生环境中的作用。该提议代表了一种新的合成方法,
光学物理学和少突胶质细胞生物学的前沿方法,并在以下方面开辟了新天地:
了解灰质和白色少突胶质细胞可塑性调节的机制,
再生
项目成果
期刊论文数量(0)
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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Ethan Garrett Hughes其他文献
Ethan Garrett Hughes的其他文献
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{{ truncateString('Ethan Garrett Hughes', 18)}}的其他基金
Precision of Myelin Plasticity in Health and Disease
健康和疾病中髓磷脂可塑性的精确性
- 批准号:
10345911 - 财政年份:2021
- 资助金额:
$ 58.63万 - 项目类别:
Precision of Myelin Plasticity in Health and Disease
健康和疾病中髓磷脂可塑性的精确性
- 批准号:
10529323 - 财政年份:2021
- 资助金额:
$ 58.63万 - 项目类别:
The role of myelination in cortical circuit function and motor behavior
髓鞘形成在皮质回路功能和运动行为中的作用
- 批准号:
10307999 - 财政年份:2020
- 资助金额:
$ 58.63万 - 项目类别:
The role of myelination in cortical circuit function and motor behavior
髓鞘形成在皮质回路功能和运动行为中的作用
- 批准号:
10087980 - 财政年份:2020
- 资助金额:
$ 58.63万 - 项目类别:
The role of myelination in cortical circuit function and motor behavior
髓鞘形成在皮质回路功能和运动行为中的作用
- 批准号:
10524761 - 财政年份:2020
- 资助金额:
$ 58.63万 - 项目类别:
Oligodendrocytes and their Precursors in a Novel Model of Antibody-Mediated Cortical Demyelination
抗体介导的皮质脱髓鞘新模型中的少突胶质细胞及其前体
- 批准号:
9507374 - 财政年份:2018
- 资助金额:
$ 58.63万 - 项目类别:
NG2 cell dynamics in the normal and injured adult central nervous system
正常和受损成人中枢神经系统中的 NG2 细胞动力学
- 批准号:
8201323 - 财政年份:2011
- 资助金额:
$ 58.63万 - 项目类别:
NG2 cell dynamics in the normal and injured adult central nervous system
正常和受损成人中枢神经系统中的 NG2 细胞动力学
- 批准号:
8318445 - 财政年份:2011
- 资助金额:
$ 58.63万 - 项目类别:
The role of astrocytes in inhibitory synaptogenesis
星形胶质细胞在抑制性突触发生中的作用
- 批准号:
7661597 - 财政年份:2007
- 资助金额:
$ 58.63万 - 项目类别:
The role of astrocytes in inhibitory synaptogenesis
星形胶质细胞在抑制性突触发生中的作用
- 批准号:
7591798 - 财政年份:2007
- 资助金额:
$ 58.63万 - 项目类别:
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