Related Experiment Video
Updated: Jul 16, 2026
In vivo Imaging of Optic Nerve Fiber Integrity by Contrast-Enhanced MRI in Mice
Published on: July 22, 2014
Inhibition of DAT function attenuates manganese accumulation in the globus pallidus
Joel G Anderson1, Paula T Cooney, Keith M Erikson
1Department of Nutrition, The University of North Carolina at Greensboro, Greensboro, NC 27402.
Abstract:
Manganese (Mn) is an essential nutrient, though exposure to high concentrations may result in neurotoxicity characterized by alterations in dopamine neurobiology. To date, it remains elusive how and why Mn targets dopaminergic neurons although recently the role of the dopamine transporter has been suggested. Our primary goal of this study was to examine the potential roles of the monoamine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET), in neuronal Mn transport. Using striatal synaptosomes, we found that only inhibition of DAT significantly decreased Mn accumulation. Furthermore, weanling rats chronically exposed to Mn, significantly accumulated Mn in several brain regions. However, rats receiving the specific DAT inhibitor GBR12909 (1 mg/kg bw, three times/week; four weeks) had significantly lower Mn levels only in the globus pallidus compared to saline-treated rats (p<0.05). Our data show that inhibition of DAT exclusively inhibits Mn accumulation in the globus pallidus during chronic exposure.
Insights
Manganese (Mn) neurotoxicity may involve dopamine transporter (DAT) mechanisms. Inhibiting DAT reduced Mn accumulation in rat brain regions, particularly the globus pallidus, suggesting DAT
Area of Science:
- Neuroscience
- Toxicology
- Neurobiology
Background:
- Manganese (Mn) is essential but toxic at high levels, affecting dopamine systems.
- The precise mechanisms of Mn neurotoxicity, especially targeting dopaminergic neurons, are not fully understood.
- The dopamine transporter (DAT) has been implicated in Mn neurotoxicity.
Purpose of the Study:
- To investigate the role of monoamine transporters, specifically dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET), in neuronal manganese transport.
- To determine if DAT inhibition affects Mn accumulation in vivo.
Main Methods:
- Utilized striatal synaptosomes to assess Mn uptake with and without monoamine transporter inhibitors.
- Administered chronic manganese exposure to weanling rats.
- Treated rats with a specific DAT inhibitor (GBR12909) and measured Mn levels in brain regions.
Main Results:
- Inhibition of DAT significantly reduced Mn accumulation in striatal synaptosomes.
- Chronic Mn exposure led to significant Mn accumulation in multiple brain regions of rats.
- DAT inhibition (GBR12909) resulted in significantly lower Mn levels exclusively in the globus pallidus.
Conclusions:
- Dopamine transporter (DAT) plays a role in neuronal manganese transport.
- Inhibition of DAT specifically mitigates Mn accumulation in the globus pallidus during chronic exposure.
- These findings highlight DAT as a potential target for mitigating Mn neurotoxicity in specific brain regions.
