CIUSSS Capitale nationale logo

Microglia control neuronal network excitability via BDNF signalling.

Publication Type:

Journal Article

Source:

Neural Plast, Volume 2013, p.429815 (2013)

Keywords:

Animals, Brain-Derived Neurotrophic Factor, Microglia, Nerve Net, Neurons, Signal Transduction, Symporters

Abstract:

<p>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.</p>

Financement / Soutien / Partenaires

logo FRQ-S logo ctrn logo fci logo cihr irsc logo nserc logo MESISentinelle nord