PMID- 24089642
OWN - NLM
STAT- MEDLINE
DCOM- 20131230
LR  - 20240324
IS  - 1687-5443 (Electronic)
IS  - 2090-5904 (Print)
IS  - 1687-5443 (Linking)
VI  - 2013
DP  - 2013
TI  - Microglia control neuronal network excitability via BDNF signalling.
PG  - 429815
LID - 10.1155/2013/429815 [doi]
LID - 429815
AB  - Microglia-neuron interactions play a crucial role in several neurological 
      disorders characterized by altered neural network excitability, such as epilepsy 
      and neuropathic pain. While a series of potential messengers have been postulated 
      as substrates of the communication between microglia and neurons, including 
      cytokines, purines, prostaglandins, and nitric oxide, the specific links between 
      messengers, microglia, neuronal networks, and diseases have remained elusive. 
      Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an 
      exception in this riddle. Here, we review the current knowledge on the role 
      played by microglial BDNF in controlling neuronal excitability by causing 
      disinhibition. The efforts made by different laboratories during the last decade 
      have collectively provided a robust mechanistic paradigm which elucidates the 
      mechanisms involved in the synthesis and release of BDNF from microglia, the 
      downstream TrkB-mediated signals in neurons, and the biophysical mechanism by 
      which disinhibition occurs, via the downregulation of the K(+)-Cl(-) cotransporter 
      KCC2, dysrupting Cl(-) homeostasis, and hence the strength of GABA(A)- and glycine 
      receptor-mediated inhibition. The resulting altered network activity appears to 
      explain several features of the associated pathologies. Targeting the molecular 
      players involved in this canonical signaling pathway may lead to novel 
      therapeutic approach for ameliorating a wide array of neural dysfunctions.
FAU - Ferrini, Francesco
AU  - Ferrini F
AD  - Department of Veterinary Sciences, University of Turin, Grugliasco, 10095 Turin, 
      Italy.
FAU - De Koninck, Yves
AU  - De Koninck Y
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130905
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Symporters)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Microglia/*metabolism
MH  - Nerve Net/metabolism/*physiology
MH  - Neurons/*metabolism
MH  - Signal Transduction/*physiology
MH  - Symporters/metabolism
MH  - K Cl- Cotransporters
PMC - PMC3780625
EDAT- 2013/10/04 06:00
MHDA- 2014/01/01 06:00
PMCR- 2013/09/05
CRDT- 2013/10/04 06:00
PHST- 2013/06/08 00:00 [received]
PHST- 2013/07/28 00:00 [accepted]
PHST- 2013/10/04 06:00 [entrez]
PHST- 2013/10/04 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
PHST- 2013/09/05 00:00 [pmc-release]
AID - 10.1155/2013/429815 [doi]
PST - ppublish
SO  - Neural Plast. 2013;2013:429815. doi: 10.1155/2013/429815. Epub 2013 Sep 5.