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Melatonin fails to protect against long-term MPTP-Induced dopamine depletion in mouse striatum

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Abstract

Several laboratories recently have reported that melatonin may possess neuroprotective properties. The present paper presents the results of our studies on the long-termin vivo effects of melatonin in a well-defined neurotoxicity model using 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in the C57BL/6 mouse. MPTP is bioactivated by brain monoamine oxidase B (MAO-B) to its neurotoxic pyridinium metabolite l-methyl-4-phenylpyridi-nium (MPP+) which destroys dopaminergic nerve terminals leading to the depletion of neostriatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC). Our initial study compared striatal DA and DOPAC levels in MPTP-only-treated animals and animals treated with melatonin 30 min prior to and 3 times hourly post-MPTP. DA/DOPAC levels measured 7 days after MPTP were similar in both groups. A second study was designed to address the possibility that melatonin cleared from the brain prior to MPP+. Animals, that had been administered the same regimen of melatonin as in the first study plus a fourth post-MPTP melatonin dose, were maintained on melatonin in drinking water until 5 days post-MPTP. Striatal DA/DOPAC levels of these melatonin-plus-MPTP treated animals also were the same as the MPTP-only-treated animals.In vitro studies confirmed that melatonin is not an inhibitor of MAO-B. These data demonstrate that melatonin does not have any significant protective effects against the long-term striatal DA and DOPAC depletion induced by MPTP in the C57BL/6 mouse.

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Authors and Affiliations

  1. Harvey W. Peters Center, Department of Chemistry, Virginia Polytechnic Institute and State University, 24061-0212, Blacksburg, VA, USA

    Cornelis J. van der Schyf, Kay Castagnoli, Sonya Palmer, Lisa Hazelwood & Neal Castagnoli

  2. Department of Biomedical Sciences and Pathobiology, VA-MD Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, 24061-0212, Blacksburg, VA, USA

    Cornelis J. van der Schyf

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  1. Cornelis J. van der Schyf
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  2. Kay Castagnoli
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  3. Sonya Palmer
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  4. Lisa Hazelwood
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  5. Neal Castagnoli
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Correspondence to Cornelis J. van der Schyf.

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Presented in part at the 37th annual Meeting of the Society of Toxicology, Seattle, March 1–5, 1998 (see Van der Schyfet al., 1998).

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van der Schyf, C.J., Castagnoli, K., Palmer, S. et al. Melatonin fails to protect against long-term MPTP-Induced dopamine depletion in mouse striatum. neurotox res 1, 261–269 (1999). https://doi.org/10.1007/BF03033256

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