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Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation

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 ex...

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Autores principales: Zhao, Zai-Hua, Du, Ke-Jun, Wang, Tao, Wang, Ji-Ye, Cao, Zi-Peng, Chen, Xiao-Ming, Song, Han, Zheng, Gang, Shen, Xue-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947239/
https://www.ncbi.nlm.nih.gov/pubmed/33718391
http://dx.doi.org/10.3389/fcell.2021.648261
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author Zhao, Zai-Hua
Du, Ke-Jun
Wang, Tao
Wang, Ji-Ye
Cao, Zi-Peng
Chen, Xiao-Ming
Song, Han
Zheng, Gang
Shen, Xue-Feng
author_facet Zhao, Zai-Hua
Du, Ke-Jun
Wang, Tao
Wang, Ji-Ye
Cao, Zi-Peng
Chen, Xiao-Ming
Song, Han
Zheng, Gang
Shen, Xue-Feng
author_sort Zhao, Zai-Hua
collection PubMed
description 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.
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spelling pubmed-79472392021-03-12 Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation Zhao, Zai-Hua Du, Ke-Jun Wang, Tao Wang, Ji-Ye Cao, Zi-Peng Chen, Xiao-Ming Song, Han Zheng, Gang Shen, Xue-Feng Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947239/ /pubmed/33718391 http://dx.doi.org/10.3389/fcell.2021.648261 Text en Copyright © 2021 Zhao, Du, Wang, Wang, Cao, Chen, Song, Zheng and Shen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhao, Zai-Hua
Du, Ke-Jun
Wang, Tao
Wang, Ji-Ye
Cao, Zi-Peng
Chen, Xiao-Ming
Song, Han
Zheng, Gang
Shen, Xue-Feng
Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title_full Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title_fullStr Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title_full_unstemmed Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title_short Maternal Lead Exposure Impairs Offspring Learning and Memory via Decreased GLUT4 Membrane Translocation
title_sort maternal lead exposure impairs offspring learning and memory via decreased glut4 membrane translocation
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947239/
https://www.ncbi.nlm.nih.gov/pubmed/33718391
http://dx.doi.org/10.3389/fcell.2021.648261
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