Melatonin protects nigral dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity in rats.
In the present study, the in vivo neuroprotective effects of melatonin, as an antioxidant, were assessed in Sprague-Dawley rats with a unilateral lesion of substantia nigra (SN) caused by a stereotaxic injection of neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). When expressed as a percentage ratio of lesioned to intact side, increased lipid peroxidation product (malondialdehyde, MDA, 117% of control) and decreased tyrosine hydroxylase (TH) enzyme activity (60% of control) in SN were observed 4 h after MPP+ lesion. In contrast, however, melatonin treatment prevented MPP+ neurotoxicity by the almost complete recovery of MDA (99% of control) and TH levels (96% of control), indicating the potent antioxidative effects of melatonin. In addition, further reduction of TH enzyme activity (52% of control) was seen 1 week after MPP+ infusion. Continuous (twice a day for 5 days), not acute (4 h) treatment with melatonin produced the partial, but not statistically significant, recovery of TH enzyme activity (71% of control), when sacrificed 1 week after MPP+ lesion. Taken together, the present results support the hypothesis that melatonin may provide the useful therapeutic strategies for the treatment of oxidative stress-induced neurodegenerative disease such as Parkinson's disease (PD).
Jin
B K
BK
Department of Biochemistry, College of Medicine, Kyung Hee University and Kohwang Medical Research Institute, Seoul, South Korea.
Shin
D Y
DY
Jeong
M Y
MY
Gwag
M R
MR
Baik
H W
HW
Yoon
K S
KS
Cho
Y H
YH
Joo
W S
WS
Kim
Y S
YS
Baik
H H
HH
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D000975:Antioxidants; D015259:Dopamine Agents; D008550:Melatonin; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine