Treatment with the spin-trap agent alpha-phenyl-N-tert-butyl nitrone does not enhance the survival of embryonic or adult dopamine neurons.
Reactive oxygen species are thought to be involved in the death of dopaminergic neurons in Parkinson's disease as well as in transplanted embryonic dopaminergic neurons. The spin-trap agent alpha-phenyl-N-tert-butyl nitrone (PBN) reacts directly with radical species and may thereby prevent them from damaging important cellular molecules such as membrane lipids. We found that PBN does not increase the survival of cultured embryonic dopaminergic neurons subjected to serum deprivation, whereas the antioxidant and lipid peroxidation inhibitor lazaroid U-83836E does. Moreover, PBN does not increase the survival of grafted embryonic dopaminergic neurons or graft efficacy (monitored as changes in drug-induced motor asymmetry in hemiparkinsonian rats) when the spin-trap agent is given intraperitoneally to the graft recipient or is added to the solutions used when preparing tissue for transplantation. Another spin-trap agent, alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN) also failed to protect neurons when given to graft recipients in the same experimental paradigm. Finally, we found that adult nigral neurons subjected to a progressive retrograde 6-OHDA lesion are not protected by systemic treatment with PBN. Even though reduction of oxidative stress by overexpression of superoxide dismutase or addition of lazaroids have previously been shown to enhance the survival of cultured and grafted dopaminergic neurons, spin-trap agents PBN and POBN do not provide protection in these experimental paradigms. This may be due to antioxidants and spin-trap agents interfering in different steps of free radical-induced cell damage.
Karlsson
J
J
Wallenberg Neuroscience Center, Section for Neuronal Survival, Department of Physiology and Neuroscience, Lund University, Sölvegatan 17, S-223 62, Lund, Sweden. jenny.karlsson@mphy.lu.se
Emgârd
M
M
Rosenblad
C
C
Brundin
P
P
D000375:Aging / Q000502:physiology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017690:Cell Transplantation; D002478:Cells, Cultured; D003497:Cyclic N-Oxides; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013378:Substantia Nigra / Q000473:pathology
D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D004298:Dopamine