Caspase-3 activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice

In 1-methyl-4-phenyl-1,2,3.6-tetrahydropyridine (MPTP) models of Parkinson' s disease (PD), dopaminergic (DA) neurons have been shown to die by apoptos is. Moreover, recent postmortem and in vitro results have indicated that ap optotic cell death induced by 1-methyl-4-phenylpyridinium (MPP+) may be med iated by caspase-3. To establish whether caspase-3 activation may indeed pl ay a role in an in vivo model of PD, we studied caspase-3 activation in C57 B1/6 mice: sub chronically intoxicated with MPTP. We show that caspase-3 ac tivation peaks early, at days 1 and 2 after the end of MPTP intoxication. I n contrast, pycnotic neurons persist until day 7 postintoxication, indicati ng that caspase-3 activation is an early and transient phenomenon in apopto tic death of DA neurons. We further demonstrate that loss of tyrosine hydro xylase (TH) immunoreactivity in this model is indeed due to cell loss rathe r than to loss of TH protein expression, We conclude that mice subchronical ly intoxicated with MPTP represent a valid PD model to study and manipulate caspase activation in vivo. (C) 2001 Movement Disorder Society.