Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data

As the aging population increases, cognitive impairment is emerging as a growing health issue worldwide. Low selenium status has been reported to correlate with cognitive decline in older adults. Nonetheless, the impact of prolonged selenium deficiency on cognitive function in adult mice and the und...

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Main Authors: Wanpeng Cheng, Yani Wang, Peiyue Sa, Luyun Liang, Lantian Zhang, Guangyan Shen, Jincheng Luo, Mengdi Li
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325007031
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author Wanpeng Cheng
Yani Wang
Peiyue Sa
Luyun Liang
Lantian Zhang
Guangyan Shen
Jincheng Luo
Mengdi Li
author_facet Wanpeng Cheng
Yani Wang
Peiyue Sa
Luyun Liang
Lantian Zhang
Guangyan Shen
Jincheng Luo
Mengdi Li
author_sort Wanpeng Cheng
collection DOAJ
description As the aging population increases, cognitive impairment is emerging as a growing health issue worldwide. Low selenium status has been reported to correlate with cognitive decline in older adults. Nonetheless, the impact of prolonged selenium deficiency on cognitive function in adult mice and the underlying mechanisms remain poorly understood. In this research, male C57BL/6 J mice were given either a normal diet (0.2 mg/kg Se) or a selenium-deficient diet (0.02 mg/kg Se) for 24 weeks to evaluate the impact of long-term selenium insufficiency on their cognitive abilities. We performed hippocampus transcriptome sequencing, real-time PCR, Golgi-Cox staining, transmission electron microscopy, western blotting, and untargeted brain metabolomics to uncover the underlying regulatory mechanism. We found that chronic selenium deficiency impaired the capabilities of object recognition, spatial memory, and self-caring in mice, and disrupted the expression of key genes related to cognitive behavior, dendrite morphogenesis, and synaptic plasticity. Additionally, prolonged selenium deficiency compromised neurite integrity, decreased dendritic spine density, impaired synaptic ultrastructure, and reduced synaptic protein expression. Brain metabolomics revealed that differential metabolites (methylmalonic acid, N-acetyl-1-aspartylglutamic acid, and S-adenosylmethionine) may be involved in the process of cognitive impairment. These findings suggest that perturbation in cognition-related transcriptome profiles, lesions in neurites and synapses, and remodeling of the brain metabolic pattern are involved in the cognitive impairment induced by long-term selenium deficiency. Our study offers a new perspective on the pathogenesis of cognitive impairment, highlighting the critical role of selenium supplementation in maintaining healthy cognitive function.
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spelling doaj-art-0568033ae40c4b9ea9d8f321edbcd2212025-08-20T03:07:50ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0129911836710.1016/j.ecoenv.2025.118367Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley DataWanpeng Cheng0Yani Wang1Peiyue Sa2Luyun Liang3Lantian Zhang4Guangyan Shen5Jincheng Luo6Mengdi Li7Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; Department of Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; Department of Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; The First Clinical College of Xuzhou Medical University, Xuzhou 221004, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; Department of Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, ChinaThe First Clinical College of Hainan Medical University, Haikou 571199, ChinaKey Laboratory for Gout Research, School of Public Health, Jiamusi University, Jiamusi 154007, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou 221004, China; Department of Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, China; Corresponding author at: Department of Anatomy, School of Basic Medical Sciences, Xuzhou Medical University, Xuzhou 221004, China.As the aging population increases, cognitive impairment is emerging as a growing health issue worldwide. Low selenium status has been reported to correlate with cognitive decline in older adults. Nonetheless, the impact of prolonged selenium deficiency on cognitive function in adult mice and the underlying mechanisms remain poorly understood. In this research, male C57BL/6 J mice were given either a normal diet (0.2 mg/kg Se) or a selenium-deficient diet (0.02 mg/kg Se) for 24 weeks to evaluate the impact of long-term selenium insufficiency on their cognitive abilities. We performed hippocampus transcriptome sequencing, real-time PCR, Golgi-Cox staining, transmission electron microscopy, western blotting, and untargeted brain metabolomics to uncover the underlying regulatory mechanism. We found that chronic selenium deficiency impaired the capabilities of object recognition, spatial memory, and self-caring in mice, and disrupted the expression of key genes related to cognitive behavior, dendrite morphogenesis, and synaptic plasticity. Additionally, prolonged selenium deficiency compromised neurite integrity, decreased dendritic spine density, impaired synaptic ultrastructure, and reduced synaptic protein expression. Brain metabolomics revealed that differential metabolites (methylmalonic acid, N-acetyl-1-aspartylglutamic acid, and S-adenosylmethionine) may be involved in the process of cognitive impairment. These findings suggest that perturbation in cognition-related transcriptome profiles, lesions in neurites and synapses, and remodeling of the brain metabolic pattern are involved in the cognitive impairment induced by long-term selenium deficiency. Our study offers a new perspective on the pathogenesis of cognitive impairment, highlighting the critical role of selenium supplementation in maintaining healthy cognitive function.http://www.sciencedirect.com/science/article/pii/S0147651325007031Selenium deficiencyCognitive impairmentTranscriptomicsNeurite morphologySynapseMetabolomics
spellingShingle Wanpeng Cheng
Yani Wang
Peiyue Sa
Luyun Liang
Lantian Zhang
Guangyan Shen
Jincheng Luo
Mengdi Li
Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
Ecotoxicology and Environmental Safety
Selenium deficiency
Cognitive impairment
Transcriptomics
Neurite morphology
Synapse
Metabolomics
title Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
title_full Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
title_fullStr Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
title_full_unstemmed Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
title_short Transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long-term selenium deficiency in miceMendeley Data
title_sort transcriptomics and metabolomics reveal the mechanism of cognitive impairment induced by long term selenium deficiency in micemendeley data
topic Selenium deficiency
Cognitive impairment
Transcriptomics
Neurite morphology
Synapse
Metabolomics
url http://www.sciencedirect.com/science/article/pii/S0147651325007031
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