Selective destruction of dopaminergic neurons by low concentrations of 6-OHDA and MPP+: protection by acetylsalicylic acid aspirin.
We optimized a mesencephalic cell culture system to employ low concentrations of 6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenylpyridinium (MPP+), neurotoxins known to trigger oxidative stress in dopaminergic cells. Both 6-OHDA and MPP(+) at 5 micro M reproducibly reduced the survival of dopaminergic neurons by 50-70% (p<0.02) without affecting the survival of the non-dopaminergic neuronal population. We found that 1mM of the non-steroidal anti-inflammatory drug (NSAID), acetylsalicylic acid (ASA), significantly (p<0.05) increased the survival of dopaminergic neurons exposed to either neurotoxin. The mechanisms underlying neuroprotection by ASA may be of therapeutic import in Parkinson's disease.
Carrasco
Emilce
E
Department of Neurology, The Albert Einstein College of Medicine, F-121N, 1300 Morris Park Ave, Bronx, NY 10461, USA.
Werner
Peter
P
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D016627:Oxidopamine; D001241:Aspirin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine