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Manganese does not alter the severe neurotoxicity of MPTP
1Department of Anatomy, Pusan National University Medical School, Busan, South Korea.
Abstract:
We utilized a mice model of Parkinsonism: (1) to evaluate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity; and (2) to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. A 2 x 3 experimental design (MPTP x+/- Mn) was as follows: SS, MPTP(-) x Mn(-); SLMn, MPTP(-) x low Mn(+); SHMn, MPTP(-) x high Mn(+); MpS, MPTP(+) x Mn(-); MpLMn, MPTP(+) x low Mn(+); MpHMn, MPTP(+) x high Mn(+). We administered MPTP (30 mg/kg per day) to male C57BL/6 mice intraperitoneally, once a day for 5 days. Subsequently, mice were treated with either 2 or 8 mg/kg of MnCl(2).4H(2)O intraperitoneally, once a day for 3 weeks. Blood and striatal Mn levels were elevated in the Mnexposed groups. The number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta were decreased significantly in the MPTP-exposed groups. The densities of TH-ir axon terminals in caudate-putamen (CPU) were significantly decreased in the MPTP-treated groups. However, Mn treatment did not affect MPTP neurotoxicity. The densities of glial fibrillary acidic protein (GFAP)-ir astrocytes in the CPU or globus pallidus were significantly increased in the MPTP-treated groups. Concentrations of dopamine in the striatum were decreased significantly in the MPTP-exposed groups only, but Mn had no effect.
Insights
Manganese exposure did not worsen 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. MPTP significantly reduced dopamine neurons and dopamine levels, but manganese did not alter these effects.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Parkinsonism is a neurodegenerative disorder characterized by the loss of dopaminergic neurons.
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that reliably induces Parkinsonism in animal models.
- Manganese (Mn) is a metal whose neurotoxicity is a growing public health concern.
Purpose of the Study:
- To evaluate the neurotoxic effects of MPTP in a mouse model.
- To determine if manganese exposure influences MPTP-induced neurotoxicity.
Main Methods:
- Mice were exposed to MPTP and varying doses of manganese chloride.
- Tyrosine hydroxylase (TH)-immunoreactive neurons and axon terminals were quantified.
- Glial fibrillary acidic protein (GFAP)-ir astrocytes were assessed.
- Dopamine concentrations in the striatum were measured.
Main Results:
- MPTP exposure significantly decreased TH-ir neurons in the substantia nigra and TH-ir axon terminals in the caudate-putamen.
- MPTP exposure significantly reduced striatal dopamine concentrations.
- Manganese exposure elevated blood and striatal Mn levels but did not affect MPTP-induced neurotoxicity.
- MPTP treatment increased GFAP-ir astrocytes in the caudate-putamen and globus pallidus.
Conclusions:
- MPTP induces significant dopaminergic neurotoxicity in mice, characterized by neuronal loss and dopamine depletion.
- Manganese exposure, at the tested doses, does not exacerbate MPTP-induced neurotoxicity.
- Further research is needed to understand the complex interactions between environmental toxins and neurodegenerative diseases.
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