Neuronal death in nigral grafts in the absence of poly (ADP-ribose) polymerase activation.
The exact causes of the extensive cell death in nigral transplants are still unknown. Since poly-(ADP-ribose) polymerase (PARP) overactivation has been implicated in neuronal death, we examined the effects of PARP on the survival of nigral grafts by using donor tissue from PARP knock-out or wild-type mice. Eight hours after preparation of the nigral cell suspension, cell damage was quantified by measurement of lactate dehydrogenase release, DNA fragmentation and caspase activation. At this stage, PARP deletion had no protective effect. Moreover, neither the survival of transplanted dopaminergic neurons, nor the functional recovery of hemiparkinsonian graft recipients were improved by the absence of PARP. We conclude that cell death in embryonic nigral grafts is not affected by the absence of PARP activation.
Kaminski Schierle
G S
GS
Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Sweden.
Hansson
O
O
Ferrando-May
E
E
Nicotera
P
P
Brundin
P
P
Leist
M
M
D000818:Animals; D016923:Cell Death / Q000502:physiology; D017690:Cell Transplantation / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D015151:Immunoblotting; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000637:transplantation*; D013565:Sympatholytics / Q000633:toxicity
D013565:Sympatholytics; D016627:Oxidopamine; D011065:Poly(ADP-ribose) Polymerases; D004298:Dopamine