Effects of brain-derived neurotrophic factor (BDNF) on activity mediated by NMDA receptors in rat spinal cord cultures

Brain-derived neurotrophic factor (BDNF) is involved in the differentiation and the survival of neurons. It has also been shown to be associated with the regrowth of neurons of damaged spinal cord and the modulation of ionic currents by acting on sodium channels and NMDA receptors through tyrosine kinase B (TrkB) receptors. We investigated the effects of BDNF on rhythm generation induced by disinhibition in dissociated cultures from embryonic rat spinal cord (E14), with extracellular multisite recordings (MultiElectrode Arrays, MEAs) or intracellular patch-clamp recordings. Exogenous BDNF had only minor effects on the bursting by increasing the activity during the burst. This increase of activity is suggested to be mediated by a potentiation of the postsynaptic NMDA receptors because it has been found that BDNF potentiates the NMDA-evoked depolarization in cultures incubated with BDNF for 10 min. Possible direct effects of BDNF on sodium channels were also investigated by local application of BDNF to the soma of patched neurons but no depolarization was observed. Long-term application of BDNF strongly decreased the activity during the burst and also the number of active electrodes, possibly due to a decrease in network density.

[1]  L. Mendell,et al.  Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord , 2001, The European journal of neuroscience.

[2]  R. Kalb,et al.  Brain‐Derived Neurotrophic Factor Induces Excitotoxic Sensitivity in Cultured Embryonic Rat Spinal Motor Neurons Through Activation of the Phosphatidylinositol 3‐Kinase Pathway , 2000, Journal of neurochemistry.

[3]  G. Mealing,et al.  Brain derived neurotrophic factor induction of N-methyl-D-aspartate receptor subunit NR2A expression in cultured rat cortical neurons , 1998, Neuroscience Letters.

[4]  E. Castrén,et al.  Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms* , 2002, The Journal of Biological Chemistry.

[5]  A. Konnerth,et al.  Neurotrophin-evoked rapid excitation through TrkB receptors , 1999, Nature.

[6]  E. Levine,et al.  Brain‐derived neurotrophic factor increases activity of NR2B‐containing N‐methyl‐D‐aspartate receptors in excised patches from hippocampal neurons , 2000, Journal of neuroscience research.

[7]  A. Konnerth,et al.  Neurotrophin-evoked depolarization requires the sodium channel NaV1.9 , 2002, Nature.

[8]  S. McMahon,et al.  Brain‐derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord , 2004, The European journal of neuroscience.

[9]  W. Tetzlaff,et al.  Promoting axonal regeneration in the central nervous system by enhancing the cell body response to axotomy , 2002, Journal of neuroscience research.

[10]  M. Heuschkel,et al.  The generation of rhythmic activity in dissociated cultures of rat spinal cord , 2001, The European journal of neuroscience.

[11]  Jürg Streit,et al.  Patterns of spontaneous activity in unstructured and minimally structured spinal networks in culture , 2005, Experimental Brain Research.

[12]  B. Lom,et al.  Brain-Derived Neurotrophic Factor Differentially Regulates Retinal Ganglion Cell Dendritic and Axonal Arborization In Vivo , 1999, The Journal of Neuroscience.

[13]  E. J. Bradbury,et al.  Brain-Derived Neurotrophic Factor Modulates Nociceptive Sensory Inputs and NMDA-Evoked Responses in the Rat Spinal Cord , 1999, The Journal of Neuroscience.

[14]  H. Schaible,et al.  Effect of brain-derived neurotrophic factor on the release of substance P from rat spinal cord , 2001, Neuroreport.

[15]  T. Gordon,et al.  The neurotrophin receptors, trkB and p75, differentially regulate motor axonal regeneration. , 2001, Journal of neurobiology.

[16]  R. Kalb,et al.  BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB , 2003, Journal of neurochemistry.

[17]  Jürg Streit,et al.  INaP underlies intrinsic spiking and rhythm generation in networks of cultured rat spinal cord neurons , 2004, The European journal of neuroscience.

[18]  R. Harris-Warrick,et al.  Contributions of intrinsic motor neuron properties to the production of rhythmic motor output in the mammalian spinal cord , 2000, Brain Research Bulletin.

[19]  L. Vyklický,et al.  Molecular and functional properties of synaptically activated NMDA receptors in neonatal motoneurons in rat spinal cord slices , 2000, The European journal of neuroscience.

[20]  P. Renaud,et al.  Spatiotemporal characterization of rhythmic activity in rat spinal cord slice cultures , 2001, The European journal of neuroscience.

[21]  L. Butcher,et al.  Induction of apoptosis by the low-affinity NGF receptor. , 1993, Science.

[22]  Jürg Streit,et al.  Contributions of NMDA receptors to network recruitment and rhythm generation in spinal cord cultures , 2004, The European journal of neuroscience.