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Nigral biochemical and structural alterations following subacute exposure to MPTP in mice
R Henry1,2, A N Agbon1, S A Musa1,3
1Neuroanatomy and Neuroscience Research Unit, Department of Human Anatomy, College of Medical Sciences, Ahmadu Bello University, Zaria, Kaduna, Nigeria.
Background:
The substantia nigra is the critical part of the midbrain responsible for movement-related functions. Nigral alterations have been associated with neurological conditions related to movement disorders, including Parkinson's disease (PD). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a toxin commonly used as a model of PD due to its selective nature of destroying dopaminergic neurons. However, toxicity varies among different animals and strains. Therefore, this study aimed to assess a comprehensive multi-level profile of early dopaminergic dysfunction by evaluating behavioural, biochemical, mitochondrial, neuroinflammatory, and histological assessments to characterise early nigrostriatal alterations in Swiss mice following subacute MPTP exposure.
Methodology:
Twelve (12) adult male mice were randomly divided into two groups of six (6) mice each. Group I (control) was administered normal saline (1 ml/kg i.p.), while group II was administered MPTP (30 mg/kg i.p.) daily for 5 consecutive days. Twenty-four (24) hours following the last MPTP administration, the mice were assessed for neurobehavioural performance using the beam walk, pole, and traction test. Assessments of oxidative stress biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH)], mitochondrial complex 1 activity, neuroinflammatory markers (IL-1β and TNF-α), brain-derived neurotrophic factor (BDNF), monoamine oxidase B (MAO-B), dopamine level, and histological examination of the substantia nigra were conducted following subacute MPTP exposure.
Results:
Exposure to MPTP altered neurobehavioural performance, oxidative stress biomarkers, neuroinflammatory markers (IL-1β, TNF-α), and other assessed biochemical parameters, as evidenced by increased beam performance latency, bradykinesia, and a lower traction score. Significant (p < 0.05) increase in MDA level and decrease in SOD, CAT, and GSH were also observed. A significant (p < 0.05) increase was observed in IL-1β and TNF-α levels, and a decrease (p < 0.05) was observed in mitochondrial complex 1 activity, BDNF and dopamine levels. Nigral histological distortions were observed following MPTP exposure.
Conclusion:
These findings confirm the established alterations in neurobehavioral, physiological and morphological features in the substantia nigra of MPTP-exposed Swiss mice. The study assesses early nigral alterations after subacute MPTP exposure and supports the use of this model for investigating MPTP-induced neurotoxicity.
Insights
Subacute exposure to MPTP in Swiss mice caused early dopaminergic dysfunction, affecting neurobehavior, oxidative stress, and neuroinflammation. This study confirms MPTP-induced nigrostriatal alterations, supporting its use as a Parkinson's disease model.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- The substantia nigra is crucial for movement, and its dysfunction is linked to Parkinson's disease (PD).
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a toxin used to model PD by destroying dopaminergic neurons.
- Toxicity of MPTP varies across animal models, necessitating strain-specific assessments.
Purpose of the Study:
- To comprehensively profile early dopaminergic dysfunction in Swiss mice following subacute MPTP exposure.
- To evaluate behavioral, biochemical, mitochondrial, neuroinflammatory, and histological changes.
- To characterize early nigrostriatal alterations induced by MPTP.
Main Methods:
- Adult male Swiss mice were divided into control (saline) and MPTP-treated groups.
- MPTP (30 mg/kg) was administered daily for 5 days.
- Assessments included neurobehavioral tests, oxidative stress markers, mitochondrial complex 1 activity, neuroinflammation markers, BDNF, MAO-B, dopamine levels, and substantia nigra histology.
Main Results:
- MPTP exposure significantly altered neurobehavior, increasing latency and bradykinesia while decreasing traction.
- Biochemical analysis revealed increased oxidative stress (MDA) and neuroinflammation (IL-1β, TNF-α), with decreased antioxidant enzymes (SOD, CAT, GSH).
- Mitochondrial complex 1 activity, BDNF, and dopamine levels were significantly reduced, alongside observed nigral histological distortions.
Conclusions:
- MPTP exposure induces significant neurobehavioral, physiological, and morphological changes in the substantia nigra of Swiss mice.
- The findings confirm early nigral alterations consistent with MPTP-induced neurotoxicity.
- This study supports the utility of the MPTP-exposed Swiss mouse model for investigating Parkinson's disease pathogenesis.
