Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway
Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the resul...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024000655 |
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| author | Yunting Li Anfei Liu Kaiju Chen Lifan Li Xiaoshun Zhang Fei Zou Xingmei Zhang Xiaojing Meng |
| author_facet | Yunting Li Anfei Liu Kaiju Chen Lifan Li Xiaoshun Zhang Fei Zou Xingmei Zhang Xiaojing Meng |
| author_sort | Yunting Li |
| collection | DOAJ |
| description | Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 μg/L vs. 60.92 μg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity. |
| first_indexed | 2024-03-07T23:39:53Z |
| format | Article |
| id | doaj.art-fb4cc86e43bf41928fecd3a7421f5379 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-03-07T23:39:53Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
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| series | Environment International |
| spelling | doaj.art-fb4cc86e43bf41928fecd3a7421f53792024-02-20T04:18:27ZengElsevierEnvironment International0160-41202024-02-01184108479Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathwayYunting Li0Anfei Liu1Kaiju Chen2Lifan Li3Xiaoshun Zhang4Fei Zou5Xingmei Zhang6Xiaojing Meng7Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, ChinaDepartment of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China; Corresponding author at: Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, 1838 Guangzhoudadaobei, Guangzhou 510515, China.Lead is an environmentally widespread neurotoxic pollutant. Although the neurotoxicity of lead has been found to be closely associated with metabolic disorders, the effects of short-chain fatty acids on the neurotoxicity of lead and its mechanisms have not yet been explored. In this study, the results of open field tests and Morris water maze tests demonstrated that chronic lead exposure caused learning and memory deficits and anxiety-like symptoms in mice. The serum butyric acid content of lead-treated mice decreased in a dose-dependent manner, and oral administration of butyrate significantly improved cognitive memory impairment and anxiety symptoms in lead-exposed mice. Moreover, butyrate alleviated neuroinflammation caused by lead exposure by inhibiting the STAT3 signaling in microglia. Butyrate also promoted the expression of acetyl-CoA synthetase ACSS2 in hippocampal neurons, thereby increasing the content of acetyl-CoA and restoring the expression of both histone H3K9ac and the downstream BDNF. We also found that the median butyric acid concentration in high-lead exposure humans was remarkably lower than that in the low-lead exposure humans (45.16 μg/L vs. 60.92 μg/L, P < 0.01), and that butyric acid significantly mediated the relationship of lead exposure with the Montreal cognitive assessment scores, with a contribution rate of 27.57 %. In conclusion, our results suggest that butyrate supplementation is a possible therapeutic strategy for lead-induced neurotoxicity.http://www.sciencedirect.com/science/article/pii/S0160412024000655PbNeurotoxicityButyrateACSS2Histone acetylation |
| spellingShingle | Yunting Li Anfei Liu Kaiju Chen Lifan Li Xiaoshun Zhang Fei Zou Xingmei Zhang Xiaojing Meng Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway Environment International Pb Neurotoxicity Butyrate ACSS2 Histone acetylation |
| title | Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway |
| title_full | Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway |
| title_fullStr | Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway |
| title_full_unstemmed | Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway |
| title_short | Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway |
| title_sort | sodium butyrate alleviates lead induced neuroinflammation and improves cognitive and memory impairment through the acss2 h3k9ac bdnf pathway |
| topic | Pb Neurotoxicity Butyrate ACSS2 Histone acetylation |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024000655 |
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