Protective role of melatonin against MPTP-induced mouse brain cell DNA fragmentation and apoptosis in vivo

G. G. Ortiz, M. Elena Crespo-López, C. Morán-Moguel, J. J. García, R. J. Reiter, D. Acuña-Castroviejo

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalNeuroendocrinology Letters
Issue number2
StatePublished - May 14 2001
Externally publishedYes


  • Apoptosis
  • DNA fragmentation
  • MPTP
  • Melatonin
  • Parkinson's disease

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Psychiatry and Mental health


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