Protective
role of melatonin against MPTP-induced mouse brain cell DNA
fragmentation and apoptosis in vivo
by Genaro
G. Ortiz, M. Elena Crespo-LÛpez, Cristina Mor·n-Moguel, JoaquÌn
J. GarcÌa, Russel J. Reiter & DarÌo AcuÒa-Castroviejo
Keywords:
melatonin, apoptosis,
DNA fragmentation, Parkinson’s disease, MPTP
Received:
January 20, 2001
Accepted: February 4, 2001
Abstract:
OBJECTIVES:
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin
that induces a Parkinsonian-type syndrome in animals which
is similar to Parkinson's disease in humans. MPTP toxicity
partially depends on the production of free radicals which
in turn play a key role in the apoptotic death of neurons.
In the present study melatonin, a potent free radical scavenger
with antiapoptotic properties, was given to determine whether
it would reduce oxidative stress in mice treated with MPTP.
MATERIALS AND METHODS: Male mice were given MPTP with or without
melatonin and the brain was studied either 6h, 24h, 7 days
or 15 days after the last MPTP injection. RESULTS: The results
show that melatonin counteracted in vivo MPTP-induced apoptosis
in midbrain neurons at 6 and 24 h after MPTP treatment, and
partially prevented apoptosis at 7 and 15 days after MPTP
administration. MPTP treatment also produced time-dependent
cell damage, whereas melatonin reduced the percentage of damaged
cells at all time points, the effect being most evident at
15 days after treatment. Moreover, melatonin counteracted
MPTP-dependent DNA fragmentation in the midbrain and striatum
at 7 and 15 days after drug administration.
CONCLUSION: These results support a role for melatonin in
protecting neurons against MPTP toxicity in vivo, and suggest
that its antiapoptotic action is one of the mechanisms by
which melatonin protects neuronal cells from neurotoxic insults.
