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CENTRAL AND PERIPHERAL EFFECT OF MPTP VIA DOSE-DEPENDENT MAGNESIUM MODULATION
R Lefter1, I M Balmus2, A Ciobica1,3,4
1Centre of Biomedical Research, Romanian Academy, Iasi, Romania.
Background:
Recent studies suggested that MPTP could cause gastrointestinal motility deficits additionally to its nonconclusive and controverted effects on the CNS (behavior and brain oxidative stress) in rats. A possible interaction between MPTP typical impairments and magnesium modulatory potential was previously suggested, as magnesium role was described in neuroprotection, gastrointestinal function, and oxidative stress.
Aim:
To investigate the possible modulatory effect of several magnesium intake formulations (via drinking water) in MPTP neurotoxicity and functional gastrointestinal impairment induction.
Materials And Methods:
Adult male Wistar rats were subjected to 3-week magnesium intake-controlled diets (magnesium depleted food and magnesium enriched drinking water) previously to acute subcutaneous MPTP treatment (30 mg/ kg body weight). Gastrointestinal motility (one hour stool collection test), and behavioral patterns (Y maze task, elevated plus maze test, open field test, forced swim test) were evaluated. Followingly, brain and bowel samples were collected, and oxidative stress was evaluated (glutathione peroxidase activity, malondial-dehyde concentrations).
Results:
MPTP could lead to magnesium intake-dependent constipation-like gastrointestinal motility impairments, anxiety- and depressive-like affective behavior changes, and mild pain tolerance defects. Also, we found similar brain and intestinal patterns in magnesium-dependent oxidative stress.
Conclusion:
While the MPTP effects in normal magnesium intake could be regarded as not fully relevant in rat models and limited to the current experimental conditions, the abnormalities observed in the affective behavior, gastrointestinal status, pain tolerance, peripheric and central oxidative status could be indicative of the extent of the systemic effects of MPTP that are not restricted to the CNS level, but also to gastro-intestinal system.
Insights
MPTP causes constipation and behavioral changes in rats, which are worsened by low magnesium. Magnesium intake may mitigate these MPTP-induced effects, highlighting its role beyond the central nervous system.
Area of Science:
- Neuroscience
- Gastroenterology
- Toxicology
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) may induce gastrointestinal motility deficits and central nervous system (CNS) effects.
- Magnesium's neuroprotective, gastrointestinal, and antioxidant roles suggest a potential interaction with MPTP-induced impairments.
Purpose of the Study:
- To investigate the modulatory effects of varied magnesium intake on MPTP neurotoxicity.
- To assess magnesium's impact on MPTP-induced functional gastrointestinal impairments.
Main Methods:
- Rats received magnesium-controlled diets and enriched drinking water before MPTP administration.
- Gastrointestinal motility, behavioral patterns (Y maze, elevated plus maze, open field, forced swim tests), and oxidative stress markers in brain and bowel were evaluated.
Main Results:
- MPTP induced magnesium intake-dependent constipation, anxiety- and depressive-like behaviors, and altered pain tolerance.
- Magnesium-dependent oxidative stress was observed in both brain and intestinal tissues.
Conclusions:
- MPTP's systemic effects extend beyond the CNS to the gastrointestinal system.
- Magnesium intake may play a crucial role in mitigating MPTP-induced abnormalities, suggesting its importance in managing neurotoxin-related conditions.
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