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Melatonin protects against 6‐OHDA‐induced neurotoxicity in rats: a role for mitochondrial complex I activity
Author(s) -
DABBENI-SALA FEDERICA,
Santo STEFANIA,
FRANCESCHINI DAVIDE,
D. SKAPER STEPHEN,
PIETRO GIUSTI AND
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0129com
Subject(s) - melatonin , substantia nigra , neuroprotection , dopaminergic , oxidative stress , mptp , dopamine , neurotoxin , chemistry , medicine , parkinsonism , endocrinology , neurotoxicity , pharmacology , biology , toxicity , disease
Unilateral injection into the right substantia nigra of the catecholaminergic neurotoxin 6‐hydroxydopamine (6‐OHDA) produces extensive loss of dopaminergic cells (‘hemi‐parkinsonian rat’). The pineal hormone melatonin, which is a potent antioxidant against different reactive oxygen species and has been reported to be neuroprotective in vivo and in vitro , was evaluated for potential anti‐Parkinson effects in this model. Imbalance in dopaminergic innervation between the striata produced by intranigral administration of 6‐OHDAresults in a postural asymmetry causing rotation away from the nonlesioned side. Melatonin given systemically prevented apomorphine‐induced circling behavior in 6‐OHDA‐lesioned rats. Reduced activity of mitochondrial oxidative phosphorylation enzymes has been suggested in some neurodegenerative diseases; in particular, selective decrease in complex I activity is observed in the substantia nigra of Parkinson's disease patients. Analysis of mitochondrial oxidative phosphorylation enzyme activities in nigral tissue from 6‐OHDA‐lesioned rats by a novel BN‐PAGE histochemical procedure revealed a clear loss of complex I activity, which was protected against in melatonintreated animals. A good correlation between behavioral parameters and enzymatic (complex I) analysis was observed independent of melatonin administration. A deficit in mitochondrial complex I could conceivably contribute to cell death in parkinsonism via free radical mechanisms, both directly via reactive oxygen species production and by decreased ATP synthesis and energy failure. Melatonin may have potential utility in the treatment of neurodegenerative disorders where oxidative stress is a participant.—Dabbeni‐Sala, F., Di Santo, S., Franceschini, D., Skaper, S. D., Giusti, P. Melatonin protects against 6‐OHDA‐induced neurotoxicity in rats: a role for mitochondrial complex I activity. FASEB J. 15, 164–170 (2001)