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