Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release

Ethylmercury (EtHg) primarily enters the body through contaminated fish and mercury-containing vaccines, raising concerns about its neurotoxic risks, particularly for infants and young children. Although its neurodevelopmental impact has been suggested, research remains inconclusive. Given that neur...

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Main Authors: Min Heui Yoo, Tae-Youn Kim, Ho-Kyong Kim, Ji-Hyun Yoo, Byoung-Seok Lee, Jae-Young Koh
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325003677
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author Min Heui Yoo
Tae-Youn Kim
Ho-Kyong Kim
Ji-Hyun Yoo
Byoung-Seok Lee
Jae-Young Koh
author_facet Min Heui Yoo
Tae-Youn Kim
Ho-Kyong Kim
Ji-Hyun Yoo
Byoung-Seok Lee
Jae-Young Koh
author_sort Min Heui Yoo
collection DOAJ
description Ethylmercury (EtHg) primarily enters the body through contaminated fish and mercury-containing vaccines, raising concerns about its neurotoxic risks, particularly for infants and young children. Although its neurodevelopmental impact has been suggested, research remains inconclusive. Given that neurite outgrowth, matrix metalloproteinase (MMP) activity, and brain-derived neurotrophic factor (BDNF) expression play critical roles in brain development and synaptic plasticity, we hypothesized that EtHg exposure disrupts these processes, leading to behavioral abnormalities. To test this hypothesis, we utilized a neonatal mouse model, exposing mice to a specific dose of EtHg comparable to potential human exposure levels. The exact dosage and exposure conditions were carefully selected to reflect real-world exposure scenarios. Our findings revealed that EtHg exposure led to significant alterations in brain development, including increased brain size and cortical thickness. These structural changes were accompanied by notable impairments in social interactions and behavioral patterns. Further analysis indicated that these effects were likely mediated by increased microglial activation and elevated BDNF expression in the cerebral cortex. Overall, our study suggests that EtHg disrupts neurodevelopment by activating microglia, leading to physiological and morphological changes in the brain. These findings highlight the need for further research on EtHg neurotoxicity and its implications for vulnerable populations, particularly infants and young children.
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spelling doaj-art-0be88bcda8eb40df9dfd74607355db7d2025-08-20T02:50:48ZengElsevierEcotoxicology and Environmental Safety0147-65132025-03-0129311803110.1016/j.ecoenv.2025.118031Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor releaseMin Heui Yoo0Tae-Youn Kim1Ho-Kyong Kim2Ji-Hyun Yoo3Byoung-Seok Lee4Jae-Young Koh5Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Sinseong-dong, Yuseong-gu, Daejeon 34114, Republic of Korea; Corresponding authors.Department of Neurology, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of KoreaDepartment of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Sinseong-dong, Yuseong-gu, Daejeon 34114, Republic of KoreaDepartment of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Sinseong-dong, Yuseong-gu, Daejeon 34114, Republic of KoreaDepartment of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Sinseong-dong, Yuseong-gu, Daejeon 34114, Republic of KoreaDepartment of Neurology, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Corresponding authors.Ethylmercury (EtHg) primarily enters the body through contaminated fish and mercury-containing vaccines, raising concerns about its neurotoxic risks, particularly for infants and young children. Although its neurodevelopmental impact has been suggested, research remains inconclusive. Given that neurite outgrowth, matrix metalloproteinase (MMP) activity, and brain-derived neurotrophic factor (BDNF) expression play critical roles in brain development and synaptic plasticity, we hypothesized that EtHg exposure disrupts these processes, leading to behavioral abnormalities. To test this hypothesis, we utilized a neonatal mouse model, exposing mice to a specific dose of EtHg comparable to potential human exposure levels. The exact dosage and exposure conditions were carefully selected to reflect real-world exposure scenarios. Our findings revealed that EtHg exposure led to significant alterations in brain development, including increased brain size and cortical thickness. These structural changes were accompanied by notable impairments in social interactions and behavioral patterns. Further analysis indicated that these effects were likely mediated by increased microglial activation and elevated BDNF expression in the cerebral cortex. Overall, our study suggests that EtHg disrupts neurodevelopment by activating microglia, leading to physiological and morphological changes in the brain. These findings highlight the need for further research on EtHg neurotoxicity and its implications for vulnerable populations, particularly infants and young children.http://www.sciencedirect.com/science/article/pii/S0147651325003677NeurotoxicityNeurite outgrowthPediatric healthMicroglial activationMegalencephaly
spellingShingle Min Heui Yoo
Tae-Youn Kim
Ho-Kyong Kim
Ji-Hyun Yoo
Byoung-Seok Lee
Jae-Young Koh
Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
Ecotoxicology and Environmental Safety
Neurotoxicity
Neurite outgrowth
Pediatric health
Microglial activation
Megalencephaly
title Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
title_full Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
title_fullStr Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
title_full_unstemmed Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
title_short Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release
title_sort assessing the health hazards of low dose ethylmercury neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain derived neurotrophic factor release
topic Neurotoxicity
Neurite outgrowth
Pediatric health
Microglial activation
Megalencephaly
url http://www.sciencedirect.com/science/article/pii/S0147651325003677
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