Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation.
Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation.
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母体铅暴露通过减少 GLUT4 膜易位损害后代的学习和记忆
DOI：
10.3389/fcell.2021.648261
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发表时间：
2021
影响因子：
5.5
通讯作者：
Shen XF
中科院分区：
文献类型：
--
作者：
Zhao ZH;Du KJ;Wang T;Wang JY;Cao ZP;Chen XM;Song H;Zheng G;Shen XF
铅（Pb）对成人和儿童均具有明显的神经毒性，导致脑功能损害。铅暴露通过突触神经毒性损害学习记忆功能，进而影响认知功能。研究表明，铅暴露在阿尔茨海默病等神经退行性疾病的病因和发病机制中起着重要作用。然而，其潜在机制仍不清楚。本研究通过建立妊娠期铅暴露（GLE）大鼠模型，探讨铅致认知功能损害的机制。我们证明，低水平的妊娠期铅暴露损害的空间学习和记忆，以及海马突触可塑性在出生后30天（PND 30）时，血铅浓度已经恢复到正常水平。铅暴露通过磷脂酰肌醇3激酶-蛋白激酶B（PI 3 K-Akt）途径降低细胞膜葡萄糖转运蛋白4（GLUT 4）水平，诱导海马葡萄糖代谢降低。在体内和体外GLUT 4过表达增加GLUT 4的膜转位和葡萄糖摄取，并逆转铅诱导的突触可塑性和认知损害。这些结果表明，铅暴露损害突触可塑性，通过降低细胞膜中的GLUT 4水平，以及葡萄糖摄取通过PI 3 K-Akt信号通路，展示了一种新的机制，铅暴露诱导的神经毒性。图形摘要
Lead (Pb) can cause a significant neurotoxicity in both adults and children, leading to the impairment to brain function. Pb exposure plays a key role in the impairment of learning and memory through synaptic neurotoxicity, resulting in the cognitive function. Researches have demonstrated that Pb exposure plays an important role in the etiology and pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease. However, the underlying mechanisms remain unclear. In the current study, a gestational Pb exposure (GLE) rat model was established to investigate the underlying mechanisms of Pb-induced cognitive impairment. We demonstrated that low-level gestational Pb exposure impaired spatial learning and memory as well as hippocampal synaptic plasticity at postnatal day 30 (PND 30) when the blood concentration of Pb had already recovered to normal levels. Pb exposure induced a decrease in hippocampal glucose metabolism by reducing glucose transporter 4 (GLUT4) levels in the cell membrane through the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) pathway. In vivo and in vitro GLUT4 over-expression increased the membrane translocation of GLUT4 and glucose uptake, and reversed the Pb-induced impairment to synaptic plasticity and cognition. These findings indicate that Pb exposure impairs synaptic plasticity by reducing the level of GLUT4 in the cell membrane as well as glucose uptake via the PI3K-Akt signaling pathway, demonstrating a novel mechanism for Pb exposure-induced neurotoxicity. Graphical Abstract
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影响因子：
3.7
作者：
Haas MA;Bell D;Slender A;Lana-Elola E;Watson-Scales S;Fisher EM;Tybulewicz VL;Guillemot F
通讯作者：
Guillemot F
影响因子：
10.4
作者：
Fox DA;Kala SV;Hamilton WR;Johnson JE;O'Callaghan JP
通讯作者：
O'Callaghan JP
影响因子：
4.2
作者：
Anderson DW;Mettil WA;Schneider JS
通讯作者：
Schneider JS
影响因子：
3.4
作者：
Bihaqi, Syed Waseem;Zawia, Nasser H.
通讯作者：
Zawia, Nasser H.
影响因子：
8.3
作者：
Hara, Azusa;Thijs, Lutgarde;Staessen, Jan A.
通讯作者：
Staessen, Jan A.