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Melatonin attenuates MPTP-induced dopaminergic neuronal injury associated with scavenging hydroxyl radical
Xue-June Li1, Jing Gu, Shi-Duo Lu
1National Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, Shanghai, China.
Abstract:
To clarify the relationship between melatonin's hydroxyl radical (*OH) scavenging ability and its protective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, in the present study, the salicylate trapping method combined with high-performance liquid chromatography (HPLC)-electrochemical detection were used to measure the contents of dihydroxybenzoic acid (DHBA) and dopamine (DA) in brain tissues of C57BL/6 mice. Immunocytohistochemistry was used to detect tyrosine hydroxylase (TH)-like positive staining neurons. Results show that MPTP treatment induced an increase in the content of DHBA and decrease in the level of DA as well as the number of TH positive stained neurons in the mouse brain. However, melatonin dose-dependently inhibited the increase of DHBA levels in ventral midbrain tissues, the decrease of DA content and the loss of dopaminergic neurons. Moreover, the relationship between the changes of DHBA and DA levels in the brain of mice following MPTP and melatonin treatment showed a statistically significant negative correlation. Present results suggest that melatonin can ameliorate MPTP-induced dopaminergic neuronal lesions probably, at least partially, because of its inhibition of *OH generation.
Insights
Melatonin protects against neuronal injury by scavenging hydroxyl radicals (*OH). This study shows melatonin reduces oxidative stress markers and preserves dopamine levels and neurons in MPTP-treated mice.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic neurotoxicity, modeling Parkinson's disease.
- Hydroxyl radicals (*OH) are implicated in MPTP-induced neuronal damage.
- Melatonin is a potent antioxidant with potential neuroprotective properties.
Purpose of the Study:
- To investigate the relationship between melatonin's hydroxyl radical (*OH) scavenging capacity and its protective effects against MPTP-induced neurotoxicity.
- To quantify the impact of melatonin on oxidative stress markers and dopaminergic neuron survival in a mouse model.
Main Methods:
- Utilized the salicylate trapping method with HPLC-electrochemical detection to measure *OH generation (via dihydroxybenzoic acid, DHBA) and dopamine (DA) levels in mouse brain tissues.
- Employed immunocytochemistry to assess the number of tyrosine hydroxylase (TH)-positive dopaminergic neurons.
- Administered MPTP to induce neurotoxicity and varied doses of melatonin for treatment.
Main Results:
- MPTP treatment significantly increased DHBA levels, decreased DA content, and reduced TH-positive neurons.
- Melatonin administration dose-dependently attenuated the MPTP-induced increase in DHBA and the decrease in DA and TH-positive neurons.
- A significant negative correlation was observed between DHBA and DA levels, supporting the role of oxidative stress.
Conclusions:
- Melatonin exhibits significant neuroprotective effects against MPTP-induced dopaminergic neurotoxicity in mice.
- Melatonin's protective mechanism is, at least in part, attributed to its ability to inhibit hydroxyl radical (*OH) generation.
- These findings highlight melatonin's therapeutic potential for neurodegenerative conditions involving oxidative stress.