Functional role of satellite glial cells in axon regeneration

卫星胶质细胞在轴突再生中的功能作用

基本信息

  • 批准号:
    9913648
  • 负责人:
  • 金额:
    $ 43.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-12-01 至 2024-11-30
  • 项目状态:
    已结题

项目摘要

ABSTRACT Identifying strategies to increase the speed and extent of axon regeneration is important for central nervous system injuries, where axon regeneration usually fails. In contrast, peripheral sensory neurons with cell body in dorsal root ganglia can switch to a regenerative state after axon injury to promote regeneration and functional recovery. Studies on the effect of nerve injury on sensory neurons have revealed multiple neuronal intrinsic signaling mechanisms that promote axon regeneration. However, virtually nothing is known about the contribution of satellite glial cells (SGC) that envelop the neuronal soma in the nerve repair process. A better understanding of the role of SGC is important and highly significant. In this proposal, we outline experiments to uncover the transcriptional changes elicited in SGC following nerve injury and establish the mechanisms by which SGC contribute to sensory neurons' regenerative abilities. SGC form a sheath that completely surround sensory neurons, resulting in each neuron together with its satellite cell sheath constituting a discrete functional unit. We know that SGCs are altered structurally and functionally under pathological conditions associated with chronic pain and communication between sensory neurons and SGC plays a critical role in nociception. Based on our preliminary studies, we have now reason to believe that SGC play a previously unrecognized role in peripheral nerve regeneration. We will reveal the transcriptional profile of SGC in response to nerve injury using single cell sequencing approaches and determine if SGC subtypes exist. We will use human DRG to determine the transcriptional profile of human SGC and their role in axon growth using co-culture approaches. These experiments will allow us to reveal if findings made in the mouse model system are predictive of the physiology of human neurons. We have also established a neuron-SGC co-culture system that allows us to visualize and quantify how SGC envelop sensory neuron soma and determine SGC's role in sensory axon growth and regeneration. Finally, we will build on our findings that SGC upregulate genes related to lipid metabolism after injury to test if de novo fatty acid synthesis in SGC affect gene expression and axon regeneration following nerve injury. We will focus on Fatty acid synthase (Fasn), the key enzyme in de novo fatty acid synthesis, which we found is upregulated in SGC after nerve injury. Fasn synthesizes palmitic acid, which is the substrate for the synthesis of more complex fatty acids, such as ether linked phospholipids (including plasmalogens). Plasmalogens are enriched in the brain and play important roles in cell signaling and differentiation and are implicated in neurological disorders. We will use genetic and lipidomics approaches to determine how lipid metabolism in SGC contribute to the axon regeneration process. Through these experiments, we will uncover the contribution of SGC and plasmalogens to nerve injury and their functional role in axon regeneration.
摘要

项目成果

期刊论文数量(0)
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Valeria Cavalli其他文献

Valeria Cavalli的其他文献

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{{ truncateString('Valeria Cavalli', 18)}}的其他基金

Unraveling the role of satellite glial cells in sensory hypersensitivity in Fragile X syndrome
揭示卫星胶质细胞在脆性 X 综合征感觉超敏反应中的作用
  • 批准号:
    10752180
  • 财政年份:
    2023
  • 资助金额:
    $ 43.09万
  • 项目类别:
Characterization of human DRG at the single cell level via integrated transcriptomics and spatial proteomics
通过整合转录组学和空间蛋白质组学在单细胞水平表征人类 DRG
  • 批准号:
    10707415
  • 财政年份:
    2022
  • 资助金额:
    $ 43.09万
  • 项目类别:
Characterization of human DRG at the single cell level via integrated transcriptomics and spatial proteomics
通过整合转录组学和空间蛋白质组学在单细胞水平表征人类 DRG
  • 批准号:
    10593846
  • 财政年份:
    2022
  • 资助金额:
    $ 43.09万
  • 项目类别:
2022 Cell Biology of the Neuron Gordon Research Conference and Gordon ReSeminar
2022年神经元细胞生物学戈登研究会议和戈登再研讨会
  • 批准号:
    9992131
  • 财政年份:
    2021
  • 资助金额:
    $ 43.09万
  • 项目类别:
Multicellular Mechanisms Driving Axon Regeneration
驱动轴突再生的多细胞机制
  • 批准号:
    10406343
  • 财政年份:
    2021
  • 资助金额:
    $ 43.09万
  • 项目类别:
Multicellular Mechanisms Driving Axon Regeneration
驱动轴突再生的多细胞机制
  • 批准号:
    10238542
  • 财政年份:
    2021
  • 资助金额:
    $ 43.09万
  • 项目类别:
Multicellular Mechanisms Driving Axon Regeneration
驱动轴突再生的多细胞机制
  • 批准号:
    10624855
  • 财政年份:
    2021
  • 资助金额:
    $ 43.09万
  • 项目类别:
Functional role of satellite glial cells in axon regeneration
卫星胶质细胞在轴突再生中的功能作用
  • 批准号:
    10061654
  • 财政年份:
    2019
  • 资助金额:
    $ 43.09万
  • 项目类别:
ELUCIDATING THE ROLE OF NEURONAL MTOR SIGNALING IN SCHWANN CELL DEVELOPMENT
阐明神经元 MTOR 信号转导在施万细胞发育中的作用
  • 批准号:
    9387143
  • 财政年份:
    2017
  • 资助金额:
    $ 43.09万
  • 项目类别:
MECHANISMS OF CHROMATIN REMODELING PROMOTING AXON REGENERATION
染色质重塑促进轴突再生的机制
  • 批准号:
    9328185
  • 财政年份:
    2016
  • 资助金额:
    $ 43.09万
  • 项目类别:

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