Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in striatal neurons but does not prevent cell death

Brain Res Bull. 2001 Oct-Nov 1;56(3-4):331-5. doi: 10.1016/s0361-9230(01)00580-9.

Abstract

In hereditary Huntington's disease, a triplet repeat disease, there is extensive loss of striatal neurons. It has been shown that brain-derived neurotrophic factor (BDNF) protects striatal neurons against a variety of insults. We confirmed that BDNF enhances survival and DARPP-32 expression in primary striatal cultures derived from postnatal mice. Furthermore, BDNF inhibited intracellular oxyradical stress triggered by dopamine, and partially blocked basal and dopamine-induced apoptosis. Nevertheless, BDNF failed to rescue striatal neurons from dopamine-induced cell death. Therefore, BDNF inhibits free radical and apoptotic pathways in medium spiny neurons, but does so downstream from the point of commitment to cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Corpus Striatum / cytology*
  • Dopamine / pharmacology*
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors / pharmacology
  • Free Radicals / metabolism
  • Huntington Disease / genetics
  • Huntington Disease / pathology
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oxidative Stress / physiology
  • Phosphoproteins / pharmacology
  • Trinucleotide Repeats

Substances

  • Brain-Derived Neurotrophic Factor
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors
  • Free Radicals
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Dopamine