7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Brain-derived neurotrophic factor enhances the excitability of rat sensory neurons through activation of the p75 neurotrophin receptor and the sphingomyelin pathway.

      1 , ,
      The Journal of physiology
      Wiley

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Neurotrophin-mediated signalling cascades can be initiated by activation of either the p75 neurotrophin receptor (p75(NTR)) or the more selective tyrosine kinase receptors. Previously, we demonstrated that nerve growth factor (NGF) increased the excitability of sensory neurons through activation of p75(NTR) to liberate sphingosine 1-phosphate. If neurotrophins can modulate the excitability of small diameter sensory neurons through activation of p75(NTR), then brain-derived neurotrophic factor (BDNF) should produce the same sensitizing action as did NGF. In this report, we show that focally applied BDNF increases the number of action potentials (APs) evoked by a ramp of depolarizing current by reducing the rheobase without altering the firing threshold. This increased excitability results, in part, from the capacity of BDNF to enhance a tetrodotoxin-resistant sodium current (TTX-R I(Na)) and to suppress a delayed rectifier-like potassium current (I(K)). The idea that BDNF acts via p75(NTR) is supported by the following observations. The sensitizing action of BDNF is prevented by pretreatment with a blocking antibody to p75(NTR) or an inhibitor of sphingosine kinase (dimethylsphingosine), but not by inhibitors of tyrosine kinase receptors (K252a or AG879). Furthermore, using single-cell RT-PCR, neurons that were sensitized by BDNF expressed the mRNA for p75(NTR) but not TrkB. These results demonstrate that neurotrophins can modulate the excitability of small diameter capsaicin-sensitive sensory neurons through the activation of p75(NTR) and its downstream sphingomyelin signalling cascade. Neurotrophins released upon activation of a variety of immuno-competent cells may be important mediators that give rise to the enhanced neuronal sensitivity associated with the inflammatory response.

          Related collections

          Author and article information

          Journal
          J. Physiol. (Lond.)
          The Journal of physiology
          Wiley
          1469-7793
          0022-3751
          Jul 01 2008
          : 586
          : 13
          Affiliations
          [1 ] Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
          Article
          jphysiol.2008.152439
          10.1113/jphysiol.2008.152439
          2538774
          18450779
          0bb1c27b-9f4b-4a20-b23b-d79d15ccdba9
          History

          Comments

          Comment on this article