Manganese exposure alters the expression of N-methyl-D-aspartate receptor subunit mRNAs and proteins in rat striatum
Related Experiment Video
Updated: Jun 16, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
1Department of Environmental Health, School of Public Health, China Medical University, North 2nd Road 92, Heping ward, Shenyang, Liaoning 110001, People's Republic of China.
Abstract:
Manganese is one of the ubiquitous environmental pollutants that can induce an indirect excitotoxicity caused by altered glutamate (Glu) metabolism. The present study has been carried out to investigate the effect of Mn on the expression of N-methyl-d-aspartate receptor (NR) subunit mRNAs and proteins in rat striatum when rats were in manganism. The rats were divided randomly into four groups of six males and six females each: control group (group 1) and 8, 40, and 200 micromol/kg Mn-treated groups (groups 2-4). The control group rats were subcutaneously (s.c.) injected with normal saline. Manganese-treated rats were s.c. injected with respectively 8, 40, and 200 micromol/kg of MnCl(2) . 6H(2)O in normal saline. The administration of MnCl(2) . 6H(2)O for 4 weeks significantly increased Mn concentration in the striatum. With the increase in administered MnCl(2) dosage, Glu concentration and cell apoptosis rate increased significantly. The relative intensity of NR2A mRNA decreased significantly in 8 micromol/kg Mn-treated rats. However, relative intensities of NR1 and NR2B mRNAs decreased significantly in 40 micromol/kg Mn-treated rats. Similarly, the relative intensity of NR2A protein showed a significant decrease in 40 micromol/kg Mn-treated rats whereas those of NR1 and NR2B decreased significantly in 200 micromol/kg Mn-treated rats. Therefore, the expression of NR2A mRNA and protein were much more sensitive to Mn than that of NR1 and NR2B. In conclusion, the results suggested that Mn induced nerve cell damage by increasing extracellular Glu level and altered expression of NR subunit mRNAs and proteins in rat striatum.
Insights
Manganese exposure alters glutamate metabolism and N-methyl-d-aspartate receptor (NR) subunit expression in rat striatum, leading to excitotoxicity and nerve cell damage. NR2A mRNA and protein are most sensitive to manganese toxicity.
Area of Science:
- Neuroscience
- Environmental Toxicology
- Molecular Biology
Background:
- Manganese (Mn) is an environmental pollutant linked to excitotoxicity via altered glutamate (Glu) metabolism.
- Manganism, a condition caused by Mn exposure, affects neurological function.
Purpose of the Study:
- To investigate the impact of manganese on N-methyl-d-aspartate (NMDA) receptor subunit mRNAs and proteins in the rat striatum.
- To understand the relationship between manganese dosage, glutamate levels, apoptosis, and NMDA receptor expression.
Main Methods:
- Rats were exposed to varying doses of manganese chloride (MnCl2) subcutaneously for 4 weeks.
- Striatal manganese concentration, glutamate levels, and cell apoptosis rates were measured.
- Expression levels of NMDA receptor (NR) subunit mRNAs (NR1, NR2A, NR2B) and proteins were analyzed.
Main Results:
- Manganese exposure significantly increased striatal Mn concentration, Glu levels, and apoptosis rate in a dose-dependent manner.
- NR2A mRNA and protein expression decreased significantly at lower Mn doses, while NR1 and NR2B showed significant decreases at higher doses.
- NR2A subunit mRNA and protein were more sensitive to manganese toxicity than NR1 and NR2B.
Conclusions:
- Manganese induces neurotoxicity by increasing extracellular glutamate and altering NMDA receptor subunit expression in the striatum.
- The differential sensitivity of NR subunits suggests specific molecular targets for manganese-induced neurodegeneration.
