Melatonin attenuates tyrosine hydroxylase loss and hypolocomotion in MPTP-lesioned rats.
Parkinson's disease is a chronic neurological disease characterized by dopaminergic neuron degeneration in the substantia nigra pars compacta. Melatonin is a powerful antioxidant agent secreted by the pineal gland which has numerous physiological functions and seems to exert an important neuroprotective effect. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model has been used to understand the pathophysiology of the disease because of its capacity to mimic biochemical and histological features observed in Parkinson's disease. This study investigated the effect of pretreatment with melatonin (50 mg/kg) on MPTP-lesioned animals 24 h and 7 days after neurotoxin infusion using the open-field test, two-way avoidance task and immunohistochemistry. Twenty-four hours after lesioning, the MPTP+vehicle group exhibited hypolocomotion and significant loss of tyrosine hydroxylase-immunoreactive cells, whereas no differences in these parameters were observed in lesioned animals receiving melatonin. Seven days after surgery, the MPTP-lesioned rats did not show hypolocomotion compared to control animals, while there was a significant dopaminergic neuronal loss. In the two-way avoidance task, MPTP-treated animals presented a cognitive deficit compared to the control groups and melatonin administration did not repair this defect. The present results suggest that melatonin reduces neuronal loss in the MPTP animal model of Parkinson's disease.
Capitelli
Caroline
C
Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Sereniki
Adriana
A
Lima
Marcelo Meira Santos
MM
Reksidler
Angela Braga
AB
Tufik
Sergio
S
Vital
Maria Aparecida Barbato Frazão
MA
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000201:enzymology* / Q000523:psychology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D014446:Tyrosine 3-Monooxygenase; D008550:Melatonin; D004298:Dopamine