Premium
Caspase‐3 activation in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice
Author(s) -
Turmel Hélène,
Hartmann Andreas,
Parain Karine,
Douhou Aicha,
Srinivasan Anu,
Agid Yves,
Hirsch Etienne C.
Publication year - 2001
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.1037
Subject(s) - mptp , dopaminergic , apoptosis , tyrosine hydroxylase , programmed cell death , caspase 3 , caspase , in vivo , parkinson's disease , chemistry , neuroscience , microbiology and biotechnology , pharmacology , biology , medicine , dopamine , biochemistry , disease
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 apoptosis. Moreover, recent postmortem and in vitro results have indicated that apoptotic cell death induced by 1‐methyl‐4‐phenylpyridinium (MPP + ) may be mediated by caspase‐3. To establish whether caspase‐3 activation may indeed play a role in an in vivo model of PD, we studied caspase‐3 activation in C57Bl/6 mice subchronically intoxicated with MPTP. We show that caspase‐3 activation peaks early, at days 1 and 2 after the end of MPTP intoxication. In contrast, pycnotic neurons persist until day 7 postintoxication, indicating that caspase‐3 activation is an early and transient phenomenon in apoptotic death of DA neurons. We further demonstrate that loss of tyrosine hydroxylase (TH) immunoreactivity in this model is indeed due to cell loss rather than to loss of TH protein expression. We conclude that mice subchronically intoxicated with MPTP represent a valid PD model to study and manipulate caspase activation in vivo. © 2001 Movement Disorder Society.