| First Author | Fleming SM | Year | 2018 |
| Journal | Neurotoxicology | Volume | 64 |
| Pages | 256-266 | PubMed ID | 28595912 |
| Mgi Jnum | J:302018 | Mgi Id | MGI:6507456 |
| Doi | 10.1016/j.neuro.2017.06.005 | Citation | Fleming SM, et al. (2018) The effect of manganese exposure in Atp13a2-deficient mice. Neurotoxicology 64:256-266 |
| abstractText | Loss of function mutations in the P5-ATPase ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis. While the function of ATP13A2 is unclear, in vitro studies suggest it is a lysosomal protein that interacts with the metals manganese (Mn) and zinc and the presynaptic protein alpha-synuclein. Loss of ATP13A2 function in mice causes sensorimotor deficits, enhanced autofluorescent storage material, and accumulation of alpha-synuclein. The present study sought to determine the effect of Mn administration on these same outcomes in ATP13A2-deficient mice. Wildtype and ATP13A2-deficient mice received saline or Mn at 5-9 or 12-19 months for 45days. Sensorimotor function was assessed starting at day 30. Autofluorescence was quantified in multiple brain regions and alpha-synuclein protein levels were determined in the ventral midbrain. Brain Mn, iron, zinc, and copper concentrations were measured in 5-9 month old mice. The results show Mn enhanced sensorimotor function, increased autofluorescence in the substantia nigra, and increased insoluble alpha-synuclein in the ventral midbrain in older ATP13A2-deficient mice. In addition, the Mn regimen used increased Mn concentration in the brain and levels were higher in Mn-treated mutants than controls. These results indicate loss of ATP13A2 function leads to increased sensitivity to Mn in vivo. |
