Nigral biochemical and structural alterations following subacute exposure to MPTP in mice.

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.