Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.
Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Alzheimer's disease, although the underlying mechanisms are unknown. Glutamate excitotoxicity has been implicated in Alzheimer's disease, Parkinson's disease, and others. We examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons from mesencephalon, the area primarily affected in Parkinson's disease. We evaluated whether these drugs protect dopaminergic neurons against excitotoxicity. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity. One hundred micro-moles ibuprofen protected both dopaminergic neurons and neurons overall against glutamate toxicity. In addition, ibuprofen alone increased the relative number of dopaminergic neurons by 47%. Thus, NSAIDs protected neurons against glutamate excitotoxicity in vitro, and deserve further consideration as neuroprotective agents in Parkinson's disease.
Casper
D
D
Department of Neurological Surgery, Neurosurgery Lab, Montefiore Medical Center, The Bronx, New York 10467, USA. casper@aecom.yu.edu
Yaparpalvi
U
U
Rempel
N
N
Werner
P
P
D000082:Acetaminophen / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002452:Cell Count / Q000706:statistics & numerical data; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D005333:Fetus; D018698:Glutamic Acid / Q000009:adverse effects* / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats
D018696:Neuroprotective Agents; D009498:Neurotoxins; D000082:Acetaminophen; D018698:Glutamic Acid; D001241:Aspirin; D004298:Dopamine; D007052:Ibuprofen