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Published on: January 7, 2014
[Protective effect of nicotinamide in a mouse Parkinson's disease model]
Jing Xu1, Sheng-quan Xu, Jie Liang
1Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Objective:
To examine the protective effect of nicotinamide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in mouse model and its mechanisms.
Methods:
Parkinson's disease was induced by injection of MPTP in adult male C57BL/6 mice, nicotinamide (500 mg/kg,i.p.) was given prior to subacute (30 mg/kg/d × 5 d,i.p.) MPTP administration. Locomotor activities, striatal dopamine levels, lactate dehydrogenase (LDH) and NO synthase (NOS) activities of whole brains and striatum were analyzed at d5 after last MPTP injections.
Results:
Pretreatment with nicotinamide significantly improved the locomotor activity in the open-field test (P<0.01), but not in the swimming test and grip & climbing test. Nicotinamide administration resulted in sparing striatal dopamine levels from MPTP-induced dopamine depletion. There was no significant difference in LDH and NOS activities in the whole brains among the groups; but the activities in the striatum were drastically elevated after MPTP treatment. Nicotinamide pretreatment markedly inhibited MPTP-induced LDH and NOS activities (P<0.01) and showed no significant difference compared to controls (P>0.05).
Conclusion:
Nicotinamide protects dopaminergic neurons against MPTP-induced neurodegeneration,which suggests that the neuroprotective effects be associated with the inhibition of cell injuries and NOS activities.
Insights
Nicotinamide pretreatment protected against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease in mice by preserving dopamine levels and inhibiting cell injury markers. This suggests a neuroprotective role for nicotinamide in Parkinson's disease models.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Context:
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons.
- The 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model is widely used to study PD pathogenesis.
- Investigating neuroprotective agents is crucial for developing effective PD treatments.
Purpose:
- To evaluate the neuroprotective effects of nicotinamide against MPTP-induced Parkinson's disease in a mouse model.
- To elucidate the underlying mechanisms of nicotinamide's potential protective action.
Summary:
- Mice were administered nicotinamide prior to MPTP to induce Parkinson's disease.
- Locomotor activity, striatal dopamine levels, and lactate dehydrogenase (LDH) and nitric oxide synthase (NOS) activities were assessed.
- Nicotinamide pretreatment significantly improved locomotor activity and preserved striatal dopamine levels, while inhibiting MPTP-induced increases in LDH and NOS activities in the striatum.
Impact:
- Nicotinamide demonstrates significant neuroprotective effects against MPTP-induced neurodegeneration in mice.
- The findings suggest that nicotinamide's protective mechanisms involve the inhibition of cellular injury and NOS activity.
- This study highlights nicotinamide as a potential therapeutic agent for Parkinson's disease.
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