Related Experiment Video
Updated: Aug 12, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Effect of manganese exposure on MPTP neurotoxicities
Sun Yong Baek1, Myong-Jong Lee, Hyun-Sil Jung
1Department of Anatomy, College of Medicine, Pusan University Hospital, Pusan, South Korea.
Abstract:
We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. We randomly assigned adult male C57BL/6 mice (n=5-7 per group) the following treatments: SO, Mn(-) x MPTP(-); MO, Mn(+) x MPTP(-); SM, Mn(-) x MPTP(+); MM, Mn(+) x MPTP(+). Mn (MnCl(2).4H(2)O) was administered intraperitoneally at a dose of 2 mg/kg daily for 3 weeks. MPTP was then administered intraperitoneally at a dose of 30 mg/kg daily for 5 days in the SM and MM groups. Seven days after the last MPTP injection, the animals were sacrificed. Blood Mn levels were elevated in the Mn-exposed groups. Striatal Mn levels were not influenced by Mn treatment alone, however, they were decreased following MPTP. Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta (SNpc) were decreased significantly in the MPTP-exposed groups. Densities of TH- and dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU) were also decreased in the MPTP-treated groups. Furthermore, glial fibrillary acidic protein (GFAP)-ir astrocytes increased in the CPU with MPTP treatment. However, no effects were observed with Mn exposure. Concentrations of dopamine (DA), 3,4-dihydrophenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the corpus striatum were also decreased significantly with MPTP treatment alone, but Mn had no effect. Thus, decreased dopaminergic activities with MPTP led to decreased DA and its metabolites. Significant hypertrophies of GFAP-ir astrocytes in the globus pallidus (GP) were observed in Mn-exposed groups, especially in the MM group. MPTP targeted dopaminergic systems whereas Mn neurotoxicities occurred in the GP. In conclusion, our data suggest that Mn does not potentiate the neurotoxicity of MPTP.
Insights
Manganese (Mn) exposure did not worsen neurotoxicity in mice treated with MPTP, a model for Parkinson's disease. While MPTP damaged dopamine systems, Mn caused separate effects in the globus pallidus.
Area of Science:
- Neuroscience
- Toxicology
- Neurodegenerative Diseases
Background:
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is crucial for studying Parkinson's disease pathogenesis.
- Manganese (Mn) is a metal with known neurotoxic potential, but its interaction with MPTP-induced neurotoxicity is not fully understood.
Purpose of the Study:
- To investigate whether concurrent manganese exposure exacerbates MPTP-induced neurotoxicity in a mouse model.
- To delineate the specific neurotoxic effects of MPTP and manganese independently and in combination.
Main Methods:
- Adult male C57BL/6 mice were divided into four groups: control (no MPTP, no Mn), Mn-only, MPTP-only, and combined Mn and MPTP exposure.
- Manganese chloride (MnCl2.4H2O) was administered intraperitoneally daily for 3 weeks; MPTP was administered daily for 5 days.
- Neurochemical and immunohistochemical analyses were performed on brain tissues, focusing on dopaminergic markers (TH, DAT), astrogliosis (GFAP), and neurotransmitter levels (DA, DOPAC, HVA).
Main Results:
- MPTP treatment significantly reduced tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars compacta (SNpc) and TH/dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU).
- MPTP exposure decreased dopamine (DA) and its metabolites (DOPAC, HVA) in the corpus striatum, indicating damage to the dopaminergic system.
- Manganese exposure alone, particularly in combination with MPTP, led to hypertrophied glial fibrillary acidic protein (GFAP)-ir astrocytes in the globus pallidus (GP), suggesting Mn-specific toxicity in this region without potentiation of MPTP effects.
Conclusions:
- Manganese exposure does not potentiate the neurotoxic effects of MPTP on the nigrostriatal dopaminergic system.
- MPTP primarily targets dopaminergic neurons, while manganese exhibits distinct neurotoxic effects, notably astrogliosis in the globus pallidus.
- This study suggests that Mn and MPTP-induced neurotoxicities are mediated through separate pathways.
