PMID- 22561407
OWN - NLM
STAT- MEDLINE
DCOM- 20121207
LR  - 20120730
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 61
IP  - 2
DP  - 2012 Jul
TI  - In vitro beneficial activation of microglial cells by mechanically-injured 
      astrocytes enhances the synthesis and secretion of BDNF through p38MAPK.
PG  - 175-86
LID - 10.1016/j.neuint.2012.04.020 [doi]
AB  - It has long been promulgated that microglial cells serve beneficial roles in the 
      central nervous system (CNS). The beneficial role of microglial cells is 
      considered to be linked with microglial activation and consequent up-regulation 
      of various trophic factors. However, what triggers microglial activation and 
      consequent elevated level of trophic factors, especially brain-derived 
      neurotrophic factor (BDNF), following traumatic CNS injury has become a crucial 
      but elusive issue. Furthermore, an effort still remains in understanding of the 
      cellular and molecular mechanisms underlying the endogenous neuroprotection of 
      activated microglial cells. In this study, we demonstrated that 
      mechanically-injured astrocyte conditioned medium (ACM) could provoke beneficial 
      activation of microglial cells and thus promote the transcription, synthesis and 
      release of BDNF in cultured microglial cells. The microglia-derived BDNF can 
      exerted a demonstrable biological role in promoting neurite outgrowth and 
      intimate terminal contacts of dorsal root ganglion (DRG) neurons co-cultured with 
      microglial cells. Moreover, ACM induced remarkable p38MAPK phosphorylation in 
      cultured microglial cells that preceded the burst of BDNF. Activating p38-MAPK by 
      anisomycin resulted in salutary effects similar to those seen with ACM, whereas 
      specific inhibition of the p38MAPK by SB203580 abrogated all the positive effects 
      of ACM, including BDNF promotion and subsequent neurite outgrowth of DRG neurite 
      outgrowth of DRG neurons and their intimate terminal contacts with microglial 
      cells. Together, our results indicated that the neuroprotection of the microglial 
      source is mainly caused by micro-environmental soluble molecules released from 
      injured astrocytes, and ACM-induced BDNF production and release from microglial 
      cells may be mediated through p38-MAPK signaling pathway. Therefore, these 
      findings may lay a foundation to further investigations on the microglial 
      beneficial activation role in the repair of traumatic CNS injury and 
      neurodegenerative diseases.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Yang, Hao
AU  - Yang H
AD  - Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, 
      China. yanghao71_99@yahoo.com
FAU - Feng, Guo-Dong
AU  - Feng GD
FAU - Liang, Zhe
AU  - Liang Z
FAU - Vitale, Angela
AU  - Vitale A
FAU - Jiao, Xi-Ying
AU  - Jiao XY
FAU - Ju, Gong
AU  - Ju G
FAU - You, Si-Wei
AU  - You SW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120425
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cells, Cultured
MH  - Fluorescent Antibody Technique
MH  - Ganglia, Spinal/growth & development/physiology
MH  - Macrophage Activation/*physiology
MH  - Microglia/*metabolism/physiology
MH  - Neurites/physiology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/physiology
MH  - Spinal Cord/cytology
MH  - Stress, Mechanical
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/*physiology
EDAT- 2012/05/09 06:00
MHDA- 2012/12/12 06:00
CRDT- 2012/05/08 06:00
PHST- 2011/10/31 00:00 [received]
PHST- 2012/03/20 00:00 [revised]
PHST- 2012/04/18 00:00 [accepted]
PHST- 2012/05/08 06:00 [entrez]
PHST- 2012/05/09 06:00 [pubmed]
PHST- 2012/12/12 06:00 [medline]
AID - S0197-0186(12)00151-9 [pii]
AID - 10.1016/j.neuint.2012.04.020 [doi]
PST - ppublish
SO  - Neurochem Int. 2012 Jul;61(2):175-86. doi: 10.1016/j.neuint.2012.04.020. Epub 
      2012 Apr 25.