Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.
Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generatin...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-02-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00021/full |
| _version_ | 1819294224127885312 |
|---|---|
| author | Lucio A Ramos-Chávez Christian R Rendón-López Daniela eSilva-Adaya Angélica eZepeda Luz M Del Razo Maria E Gonsebatt |
| author_facet | Lucio A Ramos-Chávez Christian R Rendón-López Daniela eSilva-Adaya Angélica eZepeda Luz M Del Razo Maria E Gonsebatt |
| author_sort | Lucio A Ramos-Chávez |
| collection | DOAJ |
| description | Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females. |
| first_indexed | 2024-12-24T04:22:55Z |
| format | Article |
| id | doaj.art-25ce7ff2429a4aacb9b3e89df17ccacc |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-24T04:22:55Z |
| publishDate | 2015-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-25ce7ff2429a4aacb9b3e89df17ccacc2022-12-21T17:15:45ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-02-01910.3389/fncel.2015.00021122985Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.Lucio A Ramos-Chávez0Christian R Rendón-López1Daniela eSilva-Adaya2Angélica eZepeda3Luz M Del Razo4Maria E Gonsebatt5Universidad Nacional Autónoma de MéxicoUniversidad Nacional Autónoma de MéxicoInstituto Nacional de Neurología y NeurocirugíaUniversidad Nacional Autónoma de MéxicoCINVESTAVUniversidad Nacional Autónoma de MéxicoInorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Chronic exposure to iAs has been associated with lower IQ and learning disabilities as well as memory impairment. iAs is methylated in tissues such as the brain generating mono and dimethylated species. iAs methylation requires cellular glutathione (GSH), which is the main antioxidant in the central nervous system. In humans, As species cross the placenta and are found in cord blood. A CD1 mouse model was used to investigate effects of gestational iAs exposure which can lead to oxidative damage, disrupted cysteine/glutamate transport and its putative impact in learning and memory. On postnatal days (PNDs) 1, 15 and 90, the expression of membrane transporters related to GSH synthesis and glutamate transport and toxicity, such as xCT, EAAC1, GLAST and GLT1, as well as LAT1, were analyzed. Also, the expression of the glutamate receptor N-methyl-D-aspartate (NMDAR) subunits NR2A and B as well as the presence of As species in cortex and hippocampus were investigated. On PND 90, an object location task was performed to associate exposure with memory impairment. Gestational exposure to iAs affected the expression of cysteine/glutamate transporters in cortex and hippocampus and induced a negative modulation of NMDAR NR2B subunit in the hippocampus. Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00021/fullArsenicToxicologyembryogestational exposureGSHplace memory |
| spellingShingle | Lucio A Ramos-Chávez Christian R Rendón-López Daniela eSilva-Adaya Angélica eZepeda Luz M Del Razo Maria E Gonsebatt Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. Frontiers in Cellular Neuroscience Arsenic Toxicology embryo gestational exposure GSH place memory |
| title | Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. |
| title_full | Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. |
| title_fullStr | Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. |
| title_full_unstemmed | Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. |
| title_short | Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment. |
| title_sort | neurological effects of inorganic arsenic exposure altered cysteine glutamate transport nmda expression and spatial memory impairment |
| topic | Arsenic Toxicology embryo gestational exposure GSH place memory |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2015.00021/full |
| work_keys_str_mv | AT lucioaramoschavez neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment AT christianrrendonlopez neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment AT danielaesilvaadaya neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment AT angelicaezepeda neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment AT luzmdelrazo neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment AT mariaegonsebatt neurologicaleffectsofinorganicarsenicexposurealteredcysteineglutamatetransportnmdaexpressionandspatialmemoryimpairment |