PMID- 25171395
OWN - NLM
STAT- MEDLINE
DCOM- 20150609
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 34
IP  - 3
DP  - 2014
TI  - Positive feedback loop of autocrine BDNF from microglia causes prolonged 
      microglia activation.
PG  - 715-23
LID - 10.1159/000363036 [doi]
AB  - 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)-alpha. 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-alpha 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-alpha. Microglial activation is inhibited following the sequestration of 
      endogenous BDNF, resulting in impaired microglial migration and decreased TNF-alpha 
      release. Furthermore, exogenous BDNF can also activate microglia to subsequently 
      enhance migration and increase TNF-alpha 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.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People's 
      Hospital, Shanghai, China.
FAU - Zeng, Lulu
AU  - Zeng L
FAU - Yu, Tingting
AU  - Yu T
FAU - Xu, Yongming
AU  - Xu Y
FAU - Pu, Shaofeng
AU  - Pu S
FAU - Du, Dongping
AU  - Du D
FAU - Jiang, Wei
AU  - Jiang W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140818
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line
MH  - *Feedback
MH  - In Vitro Techniques
MH  - Mice
MH  - Microglia/*metabolism
EDAT- 2014/08/30 06:00
MHDA- 2015/06/10 06:00
CRDT- 2014/08/30 06:00
PHST- 2014/06/27 00:00 [accepted]
PHST- 2014/08/30 06:00 [entrez]
PHST- 2014/08/30 06:00 [pubmed]
PHST- 2015/06/10 06:00 [medline]
AID - 000363036 [pii]
AID - 10.1159/000363036 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2014;34(3):715-23. doi: 10.1159/000363036. Epub 2014 Aug 
      18.