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Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.

Publication ,  Journal Article
Zhang, X; Zeng, L; Yu, T; Xu, Y; Pu, S; Du, D; Jiang, W
Published in: Cell Physiol Biochem
2014

BACKGROUND/AIMS: Microglia, which represent the immune cells of the central nervous system (CNS), have long been a subject of study in CNS disease research. Substantial evidence indicates that microglial activation functions as a strong neuro-inflammatory response in neuropathic pain, promoting the release of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α. In addition, activated microglia release brain-derived neurotrophic factor (BDNF), which acts as a powerful cytokine. In this study, we performed a series of in vitro experiments to examine whether a positive autocrine feedback loop existed between microglia-derived BDNF and subsequent microglial activation as well as the mechanisms underlying this positive feedback loop. METHODS: Because ATP is a classic inducer of microglial activation, firstly, we examined ATP-activated microglia in the present study. Secondly, we used TrkB/Fc, the BDNF sequester, to eliminate the effects of endogenous BDNF. ATP-stimulated microglia without BDNF was examined. Finally, we used exogenous BDNF to further determine whether BDNF could directly activate BV2 microglia. In all experiments, to quantify BV2 microglia activation, the protein levels of CD11b, a microglial activation marker, were measured by western blot. A Transwell migration assay was used to examine microglial migration. To assess the synthesis and release of proinflammatory cytokines, western blot was used to measure BDNF synthesis, and ELISA was used to quantify TNF-α release. RESULTS: In our present research, we have observed that ATP dramatically activates microglia, enhancing microglial migration, increasing the synthesis of BDNF and up-regulating the release of TNF-α. Microglial activation is inhibited following the sequestration of endogenous BDNF, resulting in impaired microglial migration and decreased TNF-α release. Furthermore, exogenous BDNF can also activate microglia to subsequently enhance migration and increase TNF-α release. CONCLUSION: Therefore, we suggest that microglial activation increases the synthesis of BDNF and that the release of BDNF can, in turn, activate microglia. A positive autocrine BDNF feedback loop from microglia may contribute to prolonged microglial activation.

Duke Scholars

Published In

Cell Physiol Biochem

DOI

EISSN

1421-9778

Publication Date

2014

Volume

34

Issue

3

Start / End Page

715 / 723

Location

Germany

Related Subject Headings

  • Physiology
  • Microglia
  • Mice
  • In Vitro Techniques
  • Feedback
  • Cell Line
  • Brain-Derived Neurotrophic Factor
  • Animals
  • Adenosine Triphosphate
  • 3101 Biochemistry and cell biology
 

Citation

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Zhang, X., Zeng, L., Yu, T., Xu, Y., Pu, S., Du, D., & Jiang, W. (2014). Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation. Cell Physiol Biochem, 34(3), 715–723. https://doi.org/10.1159/000363036
Zhang, Xin, Lulu Zeng, Tingting Yu, Yongming Xu, Shaofeng Pu, Dongping Du, and Wei Jiang. “Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.Cell Physiol Biochem 34, no. 3 (2014): 715–23. https://doi.org/10.1159/000363036.
Zhang X, Zeng L, Yu T, Xu Y, Pu S, Du D, et al. Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation. Cell Physiol Biochem. 2014;34(3):715–23.
Zhang, Xin, et al. “Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation.Cell Physiol Biochem, vol. 34, no. 3, 2014, pp. 715–23. Pubmed, doi:10.1159/000363036.
Zhang X, Zeng L, Yu T, Xu Y, Pu S, Du D, Jiang W. Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation. Cell Physiol Biochem. 2014;34(3):715–723.
Journal cover image

Published In

Cell Physiol Biochem

DOI

EISSN

1421-9778

Publication Date

2014

Volume

34

Issue

3

Start / End Page

715 / 723

Location

Germany

Related Subject Headings

  • Physiology
  • Microglia
  • Mice
  • In Vitro Techniques
  • Feedback
  • Cell Line
  • Brain-Derived Neurotrophic Factor
  • Animals
  • Adenosine Triphosphate
  • 3101 Biochemistry and cell biology