Novel mechanism for manganese regulation in the brain
NIEHS grantees showed that brain manganese is regulated by activity of the gene SLC30A10 in the digestive system. This finding provides a novel mechanism for how manganese levels are normally regulated and suggests that changes to SLC30A10 activity in the digestive system may affect neurological outcomes from manganese exposure.
Previous studies have shown that loss of function of the gene SLC30A10 in the whole body can cause manganese neurotoxicity, but how manganese is regulated is unclear. The researchers compared brain manganese levels in mice lacking SLC30A10 in the whole body to mice lacking SLC30A10 in the liver, brain, and gastrointestinal tract.
The researchers observed the unexpected result that, under normal body conditions, activity of SLC30A10 in the gastrointestinal tract and liver, and not the brain or just the liver, regulated brain manganese. They also found that expression of SLC30A10 in the brain became important when tissue manganese levels increased. With increased manganese exposure, activity of SLC30A10 in the brain reduced manganese levels and protected against neurotoxicity.
The results described previously unknown complexities in the control of manganese in the brain under normal and elevated exposure conditions. According to the authors, this might have important implications for treatment of those exposed to toxic amounts of the metal, because the work raised the possibility that drugs that enhance levels or activity of SLC30A10 in the digestive system might increase manganese excretion before it reaches the brain.
Citation: Taylor CA, Hutchens S, Liu C, Jursa T, Shawlot W, Aschner M, Smith DR, Mukhopadhyay S. 2019. SLC30A10 transporter in the digestive system regulates brain manganese under basal conditions while brain SLC30A10 protects against neurotoxicity. J Biol Chem 294(6):1860–1876.