The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice
Both excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or becau...
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MDPI AG
2023-11-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/12/1633 |
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| author | Tori R. Sides James C. Nelson Kala N. Nwachukwu Jhana Boston S. Alex Marshall |
| author_facet | Tori R. Sides James C. Nelson Kala N. Nwachukwu Jhana Boston S. Alex Marshall |
| author_sort | Tori R. Sides |
| collection | DOAJ |
| description | Both excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or because of arsenic found directly in alcoholic beverages. This study aims to determine if co-exposure to alcohol and arsenic leads to worse outcomes in neurodegeneration and associated mechanisms that could lead to cell death. To study this, mice were exposed to a 10-day gavage model of alcohol-induced neurodegeneration with varying doses of arsenic (0, 0.005, 2.5, or 10 mg/kg). The following were examined after the last dose of ethanol: (1) microglia activation assessed via immunohistochemical detection of Iba-1, (2) reactive oxygen and nitrogen species (ROS/RNS) using a colorimetric assay, (3) neurodegeneration using Fluoro-Jade<sup>®</sup> C staining (FJC), and 4) arsenic absorption using ICP-MS. After exposure, there was an additive effect of the highest dose of arsenic (10 mg/kg) in the dentate gyrus of alcohol-induced FJC+ cells. This additional cell loss may have been due to the observed increase in microglial reactivity or increased arsenic absorption following co-exposure to ethanol and arsenic. The data also showed that arsenic caused an increase in CYP2E1 expression and ROS/RNS production in the hippocampus which could have independently contributed to increased neurodegeneration. Altogether, these findings suggest a potential cyclical impact of co-exposure to arsenic and ethanol as ethanol increases arsenic absorption but arsenic also enhances alcohol’s deleterious effects in the CNS. |
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| last_indexed | 2024-03-08T20:57:12Z |
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| spelling | doaj.art-e2634ff1415e450cb23491730dd32b9d2023-12-22T13:56:55ZengMDPI AGBrain Sciences2076-34252023-11-011312163310.3390/brainsci13121633The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J MiceTori R. Sides0James C. Nelson1Kala N. Nwachukwu2Jhana Boston3S. Alex Marshall4Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USADepartment of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USADepartment of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USADepartment of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USADepartment of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USABoth excessive alcohol consumption and exposure to high levels of arsenic can lead to neurodegeneration, especially in the hippocampus. Co-exposure to arsenic and alcohol can occur because an individual with an Alcohol Use Disorder (AUD) is exposed to arsenic in their drinking water or food or because of arsenic found directly in alcoholic beverages. This study aims to determine if co-exposure to alcohol and arsenic leads to worse outcomes in neurodegeneration and associated mechanisms that could lead to cell death. To study this, mice were exposed to a 10-day gavage model of alcohol-induced neurodegeneration with varying doses of arsenic (0, 0.005, 2.5, or 10 mg/kg). The following were examined after the last dose of ethanol: (1) microglia activation assessed via immunohistochemical detection of Iba-1, (2) reactive oxygen and nitrogen species (ROS/RNS) using a colorimetric assay, (3) neurodegeneration using Fluoro-Jade<sup>®</sup> C staining (FJC), and 4) arsenic absorption using ICP-MS. After exposure, there was an additive effect of the highest dose of arsenic (10 mg/kg) in the dentate gyrus of alcohol-induced FJC+ cells. This additional cell loss may have been due to the observed increase in microglial reactivity or increased arsenic absorption following co-exposure to ethanol and arsenic. The data also showed that arsenic caused an increase in CYP2E1 expression and ROS/RNS production in the hippocampus which could have independently contributed to increased neurodegeneration. Altogether, these findings suggest a potential cyclical impact of co-exposure to arsenic and ethanol as ethanol increases arsenic absorption but arsenic also enhances alcohol’s deleterious effects in the CNS.https://www.mdpi.com/2076-3425/13/12/1633alcohol-related brain damagehippocampusarsenic toxicitymicroglial activationCYP2E1neuroimmune |
| spellingShingle | Tori R. Sides James C. Nelson Kala N. Nwachukwu Jhana Boston S. Alex Marshall The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice Brain Sciences alcohol-related brain damage hippocampus arsenic toxicity microglial activation CYP2E1 neuroimmune |
| title | The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice |
| title_full | The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice |
| title_fullStr | The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice |
| title_full_unstemmed | The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice |
| title_short | The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice |
| title_sort | influence of arsenic co exposure in a model of alcohol induced neurodegeneration in c57bl 6j mice |
| topic | alcohol-related brain damage hippocampus arsenic toxicity microglial activation CYP2E1 neuroimmune |
| url | https://www.mdpi.com/2076-3425/13/12/1633 |
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