期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.648261
关键词
lead; learning and memory; hippocampus synaptic plasticity; glucose transporter 4; PI3K-Akt
资金
- National Natural Science Foundation of China [81973073, 81273101, 81803194, 81872577, 81920108030, 81773378]
- National Basic Research Program of China (973 Program) [2012CB525002]
- Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT)
- Shaanxi Science and Technology Coordinating Innovative Project [2016KTCQ03-01]
The study found that gestational lead exposure in rats can impair spatial learning and memory, as well as hippocampal synaptic plasticity at postnatal day 30. Lead exposure induced a decrease in hippocampal glucose metabolism by reducing GLUT4 levels in the cell membrane through the PI3K-Akt pathway. Increasing GLUT4 expression reversed the lead-induced impairment in synaptic plasticity and cognition.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据