S1P-S1PR1 in bidirectional Neuron-Astrocyte communications

双向神经元-星形胶质细胞通讯中的 S1P-S1PR1

基本信息

  • 批准号:
    10710199
  • 负责人:
  • 金额:
    $ 41.7万
  • 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:
    2022-09-27 至 2027-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary/ Abstract Though synapses are formed between neurons, these structures are contacted with, ensheathed, and regulated by astrocytes. Period of neuronal synaptic connectivity and that of astrocyte maturation overlaps in developing brain. Neuronal signals instruct astrocyte differentiation and morphological maturation whereas astrocytes provide metabolic and trophic factors to support neuronal survival and growth. However, molecular mechanisms and signals that regulate neuron-astrocyte interactions and their role in neuronal circuit assembly and functions are largely unknown. We and others have previously shown that astrocytes modulate specific neural circuit formation, function and plasticity by several secreted proteins including hevin (SPARCL1), thrombospondins (TSPs), glypicans and norrin. While hevin is needed for assembly and plasticity of VGlut2+ (vesicular glutamate transporter 2) thalamocortical connections, TSPs facilitate VGlut1+ synapse formation. Intriguingly, expression of these synaptogenic proteins is developmentally regulated and are also altered in brain pathologies. Although a significant amount of research has been done to identify the neuronal receptors and mechanism of synapse formation by astrocyte-secreted synaptogenic factors SPARCL1 and TSPs, we do not know the signals and mechanisms that regulate their expression in astrocytes. We have recently found that neuronal contact stimulates expression of SPARCL1 and TSP4 via Sphingosine- 1-Phosphate (S1P)-S1P Receptor 1 (S1PR1). We also found that S1PR1 is primarily expressed by astrocytes and is localized to the fine astrocytic processes near and around the synapses and drives astrocyte morphological complexity and morphogenesis. Although, S1P-S1PR signaling is a drug target for many neurological disorders, its fundamental role in neuron-glia interactions and neuronal circuit assembly is not known. Our proposed studies will provide novel insight into the neuron-astrocyte bidirectional communication through S1P-S1PR1 axis in establishing synaptic connectivity and functions. Our detailed mechanistic studies will identify new signaling pathway downstream of S1P-S1PR1 axis in regulating calcium dynamics, glutamate sensing and expression of SPARCL1 and TSP4 in astrocytes. These studies will also advance our knowledge of how neurons regulate astrocyte development, morphogenesis and function. Moreover, these studies will decipher the mechanistic link between levels of S1P and the expression of SPARCL1 and TSP4 and clarify on the fundamental role of S1P/S1PR1 axis in the developing and diseased brain. This proposal thus is poised to provide novel mechanisms of targeting S1P/S1PR1 axis in alleviating neuropathologies.
项目摘要/摘要

项目成果

期刊论文数量(0)
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Sandeep Kumar Singh其他文献

Pharmacological Evaluation of Cordia dichotoma as Antidepressant in Experimental Animal Model
萁子抗抑郁药的实验动物模型药理评价
Isolation and identification of Leptospira species from bovines by rpoB and LipL41 genes based phylogenetic analysis
基于系统发育分析的 rpoB 和 LipL41 基因分离和鉴定牛钩端螺旋体属
  • DOI:
    10.1016/j.jksus.2020.101272
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S. Murag;D. Rathnamma;V. Balamurugan;S. Patil;Mudalagiri Dasappa Venkatesha;R. Amachawadi;A. Syed;N. Marraiki;Sandeep Kumar Singh;Shiva Prasad Kollur;C. Shivamallu
  • 通讯作者:
    C. Shivamallu
A comparative study of dielectric substrate materials effects on the performance of microstrip patch antenna for 5G/6G application
  • DOI:
    10.1007/s10854-024-13380-z
  • 发表时间:
    2024-08-22
  • 期刊:
  • 影响因子:
    2.800
  • 作者:
    Ngum Breayon Kwe;Vishal Yadav;Manish Kumar;Serguei V. Savilov;M. Z. A. Yahya;Sandeep Kumar Singh
  • 通讯作者:
    Sandeep Kumar Singh
Exploring deformation mechanisms in a refractory high entropy alloy (MoNbTaW)
探索难熔高熵合金(MoNbTaW)中的变形机制
  • DOI:
    10.1016/j.ijmecsci.2025.110000
  • 发表时间:
    2025-02-15
  • 期刊:
  • 影响因子:
    9.400
  • 作者:
    T.L. Dora;Sandeep Kumar Singh;Radha Raman Mishra;He Yu;Nitin Kishore Rawat;Akarsh Verma
  • 通讯作者:
    Akarsh Verma
Quantum dots: The cutting-edge nanotheranostics in brain cancer management
  • DOI:
    10.1016/j.jconrel.2022.08.047
  • 发表时间:
    2022-10-01
  • 期刊:
  • 影响因子:
    11.500
  • 作者:
    Pratik Chakraborty;Sabya Sachi Das;Abhijit Dey;Apala Chakraborty;Chiranjib Bhattacharyya;Ramesh Kandimalla;Biswajit Mukherjee;Abilash Valsala Gopalakrishnan;Sandeep Kumar Singh;Shubham Kant;Parma Nand;Shreesh Ojha;Pravir Kumar;Niraj Kumar Jha;Saurabh Kumar Jha;Saikat Dewanjee
  • 通讯作者:
    Saikat Dewanjee

Sandeep Kumar Singh的其他文献

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{{ truncateString('Sandeep Kumar Singh', 18)}}的其他基金

S1P-S1PR1 in bidirectional Neuron-Astrocyte communications
S1P-S1PR1 双向神经元-星形胶质细胞通讯
  • 批准号:
    10586618
  • 财政年份:
    2022
  • 资助金额:
    $ 41.7万
  • 项目类别:
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