GDNF and neublastin protect against NMDA-induced excitotoxicity in hippocampal slice cultures.
The potential neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF) and neublastin (NBN) against NMDA-induced excitotoxicity were examined in hippocampal brain slice cultures. Recombinant human GDNF (25-100 ng/ ml) or NBN, in medium conditioned by growth of transfected, NBN-producing HiB5 cells, were added to slice cultures I h before exposure to 10 microM NMDA for 48h. Neuronal cell death was monitored, before and during the NMDA exposure, by densitometric measurements of propidium iodide (PI) uptake and loss of Nissl staining. Both the addition of rhGDNF and NBN-containing medium significantly reduced the NMDA-induced PI uptake in the CA1 (p < 0.01), suggesting neuroprotective effects of these factors, beyond their well-known trophic effects on dopaminergic neurons.
Bonde
C
C
Anatomy and Neurobiology, SDU-Odense University, Ballerup, Denmark.
Kristensen
B W
BW
Blaabjerg
M
M
Johansen
T E
TE
Zimmer
J
J
Meyer
M
M
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism*; D011419:Propidium / Q000493:pharmacokinetics; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013997:Time Factors
C490886:ARTN protein, human; C490887:Artn protein, rat; D017077:Culture Media, Conditioned; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011419:Propidium; D016202:N-Methylaspartate