Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide
Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explor...
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2020.00017/full |
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| author | Daniela Silva-Adaya Daniela Silva-Adaya Lucio Antonio Ramos-Chávez Pavel Petrosyan Wendy Leslie González-Alfonso Alegna Pérez-Acosta Maria E. Gonsebatt |
| author_facet | Daniela Silva-Adaya Daniela Silva-Adaya Lucio Antonio Ramos-Chávez Pavel Petrosyan Wendy Leslie González-Alfonso Alegna Pérez-Acosta Maria E. Gonsebatt |
| author_sort | Daniela Silva-Adaya |
| collection | DOAJ |
| description | Exposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure. Mice received a single intraperitoneal injection containing 5 or 14 mg/kg sodium arsenite. Animals were killed at 2, 6, and 24 h. Significant depletion of GSH levels was observed in the cortex at 2 and 6 h, while on the striatum, hippocampus, or cerebellum regions, no significant changes were observed. GSH depletion in the cortex was associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NFκB) pathways, which led to the upregulation of xCT, excitatory amino acid carrier 1 (EAAC1), glutamate/aspartate transporter (GLAST), and glial glutamate transporter 1 (GLT-1), and the activation of the transsulfuration pathways, which led to the overproduction of H2S in the cortex and increased levels of GSH in the cortex and cerebellum at 24 h. In the cortex, the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B were also altered at 24 h. These early effects were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum. |
| first_indexed | 2024-12-22T10:11:43Z |
| format | Article |
| id | doaj.art-4c5b980ac0524dfab862ea33a409a2cf |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T10:11:43Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-4c5b980ac0524dfab862ea33a409a2cf2022-12-21T18:29:50ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022020-02-011410.3389/fncel.2020.00017509209Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen SulfideDaniela Silva-Adaya0Daniela Silva-Adaya1Lucio Antonio Ramos-Chávez2Pavel Petrosyan3Wendy Leslie González-Alfonso4Alegna Pérez-Acosta5Maria E. Gonsebatt6Departamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, MexicoLaboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, México, MexicoDepartamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Ciudad de México, México, MexicoDepartamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, MexicoDepartamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, MexicoDepartamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, MexicoDepartamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, MexicoExposure to toxic metals and metalloids is an important cause of preventable diseases worldwide. Inorganic arsenic (iAs) affects several organs and tissues, causing neurobehavioral alterations in the central nervous system (CNS) that might lead to neurodegeneration. In this work, we wanted to explore the time- and dose-related changes on glutathione (GSH) levels in several regions of the CNS, such as the cortex, striatum, hippocampus, and cerebellum, to identify the initial cellular changes associated to GSH depletion due to iAs exposure. Mice received a single intraperitoneal injection containing 5 or 14 mg/kg sodium arsenite. Animals were killed at 2, 6, and 24 h. Significant depletion of GSH levels was observed in the cortex at 2 and 6 h, while on the striatum, hippocampus, or cerebellum regions, no significant changes were observed. GSH depletion in the cortex was associated with the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NFκB) pathways, which led to the upregulation of xCT, excitatory amino acid carrier 1 (EAAC1), glutamate/aspartate transporter (GLAST), and glial glutamate transporter 1 (GLT-1), and the activation of the transsulfuration pathways, which led to the overproduction of H2S in the cortex and increased levels of GSH in the cortex and cerebellum at 24 h. In the cortex, the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B were also altered at 24 h. These early effects were not homogeneous among different brain regions and indicate early neurotoxic alterations in the cortex and cerebellum.https://www.frontiersin.org/article/10.3389/fncel.2020.00017/fullarsenicGSHNrf2NFκBCNS cysteine/glutamate transportersH2S |
| spellingShingle | Daniela Silva-Adaya Daniela Silva-Adaya Lucio Antonio Ramos-Chávez Pavel Petrosyan Wendy Leslie González-Alfonso Alegna Pérez-Acosta Maria E. Gonsebatt Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide Frontiers in Cellular Neuroscience arsenic GSH Nrf2 NFκB CNS cysteine/glutamate transporters H2S |
| title | Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide |
| title_full | Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide |
| title_fullStr | Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide |
| title_full_unstemmed | Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide |
| title_short | Early Neurotoxic Effects of Inorganic Arsenic Modulate Cortical GSH Levels Associated With the Activation of the Nrf2 and NFκB Pathways, Expression of Amino Acid Transporters and NMDA Receptors and the Production of Hydrogen Sulfide |
| title_sort | early neurotoxic effects of inorganic arsenic modulate cortical gsh levels associated with the activation of the nrf2 and nfκb pathways expression of amino acid transporters and nmda receptors and the production of hydrogen sulfide |
| topic | arsenic GSH Nrf2 NFκB CNS cysteine/glutamate transporters H2S |
| url | https://www.frontiersin.org/article/10.3389/fncel.2020.00017/full |
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