Brain-derived neurotrophic factor inhibits apoptosis and dopamine-induced free radical production in striatal neurons but does not prevent cell death.
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.
Petersén A
A
A
Section for Neuronal Survival, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Larsen
K E
KE
Behr
G G
GG
Romero
N
N
Przedborski
S
S
Brundin
P
P
Sulzer
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D004298:Dopamine / Q000494:pharmacology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010750:Phosphoproteins / Q000494:pharmacology; D018911:Trinucleotide Repeats
D019208:Brain-Derived Neurotrophic Factor; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D004791:Enzyme Inhibitors; D005609:Free Radicals; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D004298:Dopamine