NT-3 and BDNF protect CNS neurons against metabolic/excitotoxic insults

Brain Res. 1994 Mar 21;640(1-2):56-67. doi: 10.1016/0006-8993(94)91857-0.


Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) were recently shown to have biological activity in central neurons. In the present study, NT-3 and BDNF attenuated glucose deprivation-induced neuronal damage dose-dependently in rat hippocampal, septal and cortical cultures. Direct measurements of intraneuronal free calcium levels ([Ca2+]i) and manipulations of calcium influx demonstrated that NT-3 and BDNF each prevented the elevation of [Ca2+]i that mediated glucose deprivation-induced injury. Studies in cultures depleted of glia indicated a direct action of NT-3 and BDNF on neurons. Neurons pretreated with NT-3 or BDNF for 24 hr were more resistant to glutamate neurotoxicity, and showed attenuated [Ca2+]i responses to glutamate. TrkB (BDNF receptor) and trkC (NT-3 receptor) proteins were present in hippocampal, cortical and septal cultures where they were localized to neuronal cell bodies and neurites. The data demonstrate that NT-3 and BDNF can protect neurons against metabolic and excitotoxic insults, and suggest that these neurotrophins may serve [Ca2+]i-stabilizing and neuroprotective functions in the brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / cytology*
  • Brain / drug effects
  • Brain-Derived Neurotrophic Factor
  • Calcium / metabolism
  • Calcium / physiology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Culture Media
  • Glucose / physiology
  • Glutamates / toxicity
  • Glutamic Acid
  • Immunohistochemistry
  • Nerve Growth Factors / pharmacology*
  • Nerve Tissue Proteins / pharmacology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotrophin 3
  • RNA, Messenger / biosynthesis
  • Rats
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Growth Factor / biosynthesis


  • Brain-Derived Neurotrophic Factor
  • Culture Media
  • Glutamates
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neurotrophin 3
  • RNA, Messenger
  • Receptor, Ciliary Neurotrophic Factor
  • Receptors, Growth Factor
  • Glutamic Acid
  • Receptor Protein-Tyrosine Kinases
  • Glucose
  • Calcium