Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood
INTRODUCTION: Dichloroacetic acid (DCA), a by‐product of disinfection in drinking water, is a multiple organ carcinogen in humans and animals. Still, little research on its neurotoxicity and its underlying mechanism has not been elucidated. METHODS: Sprague Dawley rats were intragastrically treated...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559617/ https://www.ncbi.nlm.nih.gov/pubmed/32841551 http://dx.doi.org/10.1002/brb3.1801 |
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author | Wang, Yue Jiang, Wenbo Dong, Qiuying Zhao, Yue Chen, Yingying Sun, Changhao Sun, Guoli |
author_facet | Wang, Yue Jiang, Wenbo Dong, Qiuying Zhao, Yue Chen, Yingying Sun, Changhao Sun, Guoli |
author_sort | Wang, Yue |
collection | PubMed |
description | INTRODUCTION: Dichloroacetic acid (DCA), a by‐product of disinfection in drinking water, is a multiple organ carcinogen in humans and animals. Still, little research on its neurotoxicity and its underlying mechanism has not been elucidated. METHODS: Sprague Dawley rats were intragastrically treated with DCA at 10, 30, 90 mg/kg body weight from pregnancy till delivery. At eight weeks of age of pups, we assessed cognitive performance using the standard behavioral tests. And the hippocampus structure and ultrastructure were evaluated using light and electron microscope. The oxidative stress indicators and neuroinflammation factors were measured with the corresponding kits. The mRNA and protein of synaptic factors were detected using RT‐PCR and Western blot. RESULTS: The results indicated that maternal weight gain and offspring birthweight were not significantly affected by DCA. However, behavioral tests, including morris water maze and step down, showed varying degrees of changes in DCA‐treated pups. Additionally, we found significant differences in hippocampal neurons by histomorphological observation. Biochemical analysis results indicated superoxide dismutase (SOD) and catalase (CAT) activities, as well as reactive oxygen species (ROS), nitric oxide (NO), and reduced glutathione (GSH) levels, were affected by DCA accompanying with DNA damage. Moreover, the results showed that the neuroinflammation factors (TNF‐α, IL‐6, IL‐1β) in DCA treatment groups increased significantly compared with the control pups. And we also found that DCA treatment caused a differential modulation of proteins (BDNF, cAMP‐response element‐binding protein1 (CREB1), p‐CREB1, postsynaptic density‐95 (PSD‐95), synapsin I, p‐synapsin I), and mRNA (BDNF, PSD‐95). CONCLUSIONS: Taken together, these results above showed that oxidative stress, neuroinflammation response, and weakened synaptic plasticity in pups hippocampus induced by fetal exposure to DCA could damage the function of memory and cognition in the adulthood. |
format | Online Article Text |
id | pubmed-7559617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75596172020-10-20 Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood Wang, Yue Jiang, Wenbo Dong, Qiuying Zhao, Yue Chen, Yingying Sun, Changhao Sun, Guoli Brain Behav Original Research INTRODUCTION: Dichloroacetic acid (DCA), a by‐product of disinfection in drinking water, is a multiple organ carcinogen in humans and animals. Still, little research on its neurotoxicity and its underlying mechanism has not been elucidated. METHODS: Sprague Dawley rats were intragastrically treated with DCA at 10, 30, 90 mg/kg body weight from pregnancy till delivery. At eight weeks of age of pups, we assessed cognitive performance using the standard behavioral tests. And the hippocampus structure and ultrastructure were evaluated using light and electron microscope. The oxidative stress indicators and neuroinflammation factors were measured with the corresponding kits. The mRNA and protein of synaptic factors were detected using RT‐PCR and Western blot. RESULTS: The results indicated that maternal weight gain and offspring birthweight were not significantly affected by DCA. However, behavioral tests, including morris water maze and step down, showed varying degrees of changes in DCA‐treated pups. Additionally, we found significant differences in hippocampal neurons by histomorphological observation. Biochemical analysis results indicated superoxide dismutase (SOD) and catalase (CAT) activities, as well as reactive oxygen species (ROS), nitric oxide (NO), and reduced glutathione (GSH) levels, were affected by DCA accompanying with DNA damage. Moreover, the results showed that the neuroinflammation factors (TNF‐α, IL‐6, IL‐1β) in DCA treatment groups increased significantly compared with the control pups. And we also found that DCA treatment caused a differential modulation of proteins (BDNF, cAMP‐response element‐binding protein1 (CREB1), p‐CREB1, postsynaptic density‐95 (PSD‐95), synapsin I, p‐synapsin I), and mRNA (BDNF, PSD‐95). CONCLUSIONS: Taken together, these results above showed that oxidative stress, neuroinflammation response, and weakened synaptic plasticity in pups hippocampus induced by fetal exposure to DCA could damage the function of memory and cognition in the adulthood. John Wiley and Sons Inc. 2020-08-25 /pmc/articles/PMC7559617/ /pubmed/32841551 http://dx.doi.org/10.1002/brb3.1801 Text en © 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Wang, Yue Jiang, Wenbo Dong, Qiuying Zhao, Yue Chen, Yingying Sun, Changhao Sun, Guoli Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title | Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title_full | Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title_fullStr | Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title_full_unstemmed | Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title_short | Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
title_sort | fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559617/ https://www.ncbi.nlm.nih.gov/pubmed/32841551 http://dx.doi.org/10.1002/brb3.1801 |
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