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

Bin Cheng, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

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 inlux 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 indicateda 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 localied 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.

Original languageEnglish (US)
Pages (from-to)56-67
Number of pages12
JournalBrain Research
Volume640
Issue number1-2
DOIs
StatePublished - Mar 21 1994
Externally publishedYes

Keywords

  • Calcium
  • Excitotoxicity
  • Fura-2
  • Neurotrophin
  • TrkB
  • TrkC
  • Tyrosine kinase

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)

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