APLP1, Alzheimer's-like pathology and neurodegeneration in the frontal cortex of manganese-exposed non-human primates.
APLP1, Alzheimer's-like pathology and neurodegeneration in the frontal cortex of manganese-exposed non-human primates.
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DOI：
10.1016/j.neuro.2010.02.004
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发表时间：
2010-09
期刊：
影响因子：
3.4
通讯作者：
Guilarte TR
中科院分区：
文献类型：
--
作者：
Guilarte TR
长期接触锰 (Mn) 会产生具有精神、认知和帕金森病特征的神经综合征。暴露于不同剂量锰的食蟹猴额叶皮层的基因表达研究表明，基因表达变化与细胞周期调节、DNA修复、细胞凋亡、泛素蛋白酶体系统、蛋白质折叠、胆固醇稳态、轴突/囊泡运输和炎症相关。淀粉样蛋白-β (A-β) 前体样蛋白 1 (APLP1) 是淀粉样蛋白前体家族的成员，是上调程度最高的基因。免疫组织化学证实 APLP1 表达增加，并揭示 A-β 弥漫性斑块的存在。接触锰的动物的皮质神经元和白质纤维表现出银颗粒的积累，表明正在进行的退化。皮质神经元还表达核肥大、胞质内空泡和凋亡柱状。接触锰的组织中的神经元和神经胶质细胞中 p53 的水平增加。另一种淀粉样蛋白生成蛋白β-突触核蛋白的分析也显示出接触锰的动物的灰质和白质中的聚集。总之，非人类灵长类动物长期接触锰会产生细胞应激反应，导致神经退行性变化、额叶皮质中弥漫性 A-β 斑块和 β-突触核蛋白聚集。这些变化可能有助于解释这些动物表现出的认知和工作记忆缺陷。
Chronic manganese (Mn) exposure produces a neurological syndrome with psychiatric, cognitive and parkinsonian features. Gene expression studies in the frontal cortex of Cynomolgus macaques exposed to different doses of Mn showed gene expression changes associated with cell cycle regulation, DNA repair, apoptosis, ubiquitin-proteasome system, protein folding, cholesterol homeostasis, axonal/vesicular transport and inflammation. Amyloid-beta (A-beta) precursor-like protein 1 (APLP1), a member of the amyloid precursor family, was the most highly up-regulated gene. Immunohistochemistry confirmed increased APLP1 expression and revealed the presence of A-beta diffuse plaques. Cortical neurons and white matter fibers from Mn-exposed animals exhibited accumulation of silver grains indicative of on-going degeneration. Cortical neurons also expressed nuclear hypertrophy, intracytoplasmic vacuoles, and apoptotis stigmata. The levels of p53 were increased in neurons and glial cells in Mn-exposed tissue. Analysis of another amyloidogenic protein, -synuclein, also exhibited aggregation in the gray and white matter from Mn-exposed animals. In summary, chronic Mn exposure in non-human primates produces a cellular stress response leading to neurodegenerative changes, diffuse A-beta plaques and -synuclein aggregation in the frontal cortex. These changes may help explain the cognitive and working memory deficits expressed by these animals.
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影响因子：
10.4
作者：
Wasserman GA;Liu X;Parvez F;Ahsan H;Levy D;Factor-Litvak P;Kline J;van Geen A;Slavkovich V;LoIacono NJ;Cheng Z;Zheng Y;Graziano JH
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Graziano JH
影响因子：
3.4
作者：
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影响因子：
9.9
作者：
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通讯作者：
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影响因子：
5.1
作者：
Klos, K. J.;Chandler, M.;Josephs, K. A.
通讯作者：
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影响因子：
4.7
作者：
Guilarte, Tomas R.;Burton, Neal C.;Schneider, Jay S.
通讯作者：
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