The effect of manganese exposure in Atp13a2-deficient mice.
The effect of manganese exposure in Atp13a2-deficient mice.
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DOI：
10.1016/j.neuro.2017.06.005
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发表时间：
2018-01
期刊：
影响因子：
3.4
通讯作者：
Schultheis, Patrick J.
中科院分区：
文献类型：
--
作者：
Fleming, Sheila M.;Santiago, Nicholas A.;Mullin, Elizabeth J.;Pamphile, Shanta;Karkare, Swagata;Lemkuhl, Andrew;Ekhator, Osunde R.;Linn, Stephen C.;Holden, John G.;Aga, Diana S.;Roth, Jerome A.;Liou, Benjamin;Sun, Ying;Shull, Gary E.;Schultheis, Patrick J.
P5-ATP酶ATP 13 A2的功能缺失突变与Kufor-Rakeb综合征和神经元蜡样脂褐质沉积症相关。虽然ATP 13 A2的功能尚不清楚，但体外研究表明它是一种与金属锰（Mn）和锌以及突触前蛋白α-突触核蛋白相互作用的溶酶体蛋白。小鼠中ATP 13 A2功能的丧失导致感觉运动缺陷、增强的自发荧光储存物质和α-突触核蛋白的积累。本研究试图确定Mn给药对ATP 13 A2缺陷小鼠中这些相同结果的影响。野生型和ATP 13 A2缺陷型小鼠在5-9或12-19个月时接受盐水或Mn，持续45天。从第30天开始评估感觉运动功能。在多个脑区域中定量自体荧光，并在腹侧中脑中测定α-突触核蛋白水平。在5-9月龄小鼠中测量脑Mn、铁、锌和铜浓度。结果表明，锰增强感觉运动功能，增加黑质中的自发荧光，并增加不溶性α-突触核蛋白在腹侧中脑在老年ATP 13 A2缺陷型小鼠。此外，锰方案使用增加锰浓度在大脑中和锰处理的突变体中的水平高于对照。这些结果表明ATP 13 A2功能的丧失导致体内对Mn的敏感性增加。
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 45 days. 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.
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影响因子：
3.4
作者：
Kim, Dong-Suk;Jin, Huajun;Anantharam, Vellareddy;Gordon, Richard;Kanthasamy, Arthi;Kanthasamy, Anumantha G.
通讯作者：
Kanthasamy, Anumantha G.
影响因子：
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作者：
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
Fitsanakis, VA;Au, C;Aschner, M
通讯作者：
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