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Neuroendocrinology Letters incl. Psychoneuroimmunology & Chronobiology

 

Neuroendocrinology›Letters incl. Psychoneuroimmunology & Chronobiology,
ISSN›0172Ů780X Copyright›©›2000 Neuroendocrinology›Letters

NEL VOL. 22 No. 2
ORIGINAL ARTICLE

Full text pdf (313kb)

2001; 22:101-108
pii: NEL220201A04

PMID: 11335886


Protective role of melatonin against MPTP-induced mouse brain cell DNA fragmentation and apoptosis in vivo
by
Genaro G. Ortiz, M. Elena Crespo-LŘpez, Cristina Mor∑n-Moguel, JoaquŐn J. GarcŐa, Russel J. Reiter & DarŐo Acu“a-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.

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