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Published on: January 7, 2014
Consequences of manganese administration for striatal dopamine and motor behavior in
C A Dodd1, J R Bloomquist, B G Klein
1Department of Biology, Fort Valley State University, Fort Valley, GA, USA.
Abstract:
Environmental compounds may be important contributors to Parkinson's disease etiology. Epidemiological and experimental evidence for the facilitation of parkinsonism by manganese is equivocal. This work addressed methodological concerns in the few studies of manganese modulation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in C57BL/6 mice. Male, retired breeder mice received 0 or 100 mg/kg of manganese chloride (MnCl₂; subcutaneously on days 1, 4 and 7) and 0 or 20 mg/kg of MPTP (intraperitoneally on day 8) and survived up to day 15 or 22. On the day of sacrificing, horizontal (grid crossing) and vertical (rearing) open field movement, swimming, grip strength and grip fatigue were examined. Striata were analyzed for dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) using high-performance liquid chromatography. MPTP produced a main effect decrease in striatal dopamine (48.8%) and DOPAC (38.1%), but there was no main effect of MnCl₂ or MnCl₂ x MPTP interaction. However, modulatory interactions were observed between the effects of MnCl₂ and MPTP for grid crossing, rearing and grip strength. Interestingly, these interactions reduced the severity of behavioral deficits attributable to either of these compounds alone. For rearing and grip strength, the MnCl₂ x MPTP interaction was dependent upon survival time. The mechanistic nature of the MnCl₂ x MPTP interaction upon these behaviors, in the absence of such an interaction for striatal dopamine and DOPAC, remains to be clarified.
Insights
Manganese chloride (MnCl₂) and MPTP interactions in mice unexpectedly reduced behavioral deficits. This suggests a complex relationship between manganese exposure and MPTP-induced parkinsonism, warranting further investigation.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Environmental factors are implicated in Parkinson's disease (PD) etiology.
- Evidence linking manganese exposure to parkinsonism is inconsistent.
- Methodological limitations exist in studies of manganese and MPTP-induced neurotoxicity.
Purpose of the Study:
- To investigate the modulatory effects of manganese chloride (MnCl₂) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in C57BL/6 mice.
- To address methodological concerns in previous studies.
- To examine behavioral and neurochemical outcomes.
Main Methods:
- Mice were administered MnCl₂ and MPTP at specific doses and time points.
- Behavioral assessments included open field activity (grid crossing, rearing), swimming, and grip strength.
- Striatal dopamine and DOPAC levels were quantified using high-performance liquid chromatography.
Main Results:
- MPTP significantly decreased striatal dopamine and DOPAC levels.
- No main effect of MnCl₂ or MnCl₂ x MPTP interaction was observed on dopamine or DOPAC.
- MnCl₂ and MPTP exhibited modulatory interactions on behavioral measures (grid crossing, rearing, grip strength), reducing deficits caused by individual exposures.
- These behavioral interactions were survival time-dependent for rearing and grip strength.
Conclusions:
- Manganese chloride modulated MPTP-induced behavioral deficits in mice, but not striatal dopamine/DOPAC levels.
- The interaction between MnCl₂ and MPTP reduced the severity of certain behavioral impairments.
- The mechanisms underlying this protective interaction remain unclear and require further elucidation.
