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Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

Ramos-Chávez LA, Rendón-López CR, Zepeda A, Silva-Adaya D, Del Razo LM, Gonsebatt ME - Front Cell Neurosci (2015)

Bottom Line: In humans, As species cross the placenta and are found in cord blood.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.Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Mexico, DF, Mexico.

ABSTRACT
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 (CNS). 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.

No MeSH data available.


Related in: MedlinePlus

The effect of As exposure on the spatial working memory in the recognition place task in male and female mice on PND 90. Discrimination index (DI) = (novel place exploration time/total exploration time). (A) male and female DI of location in the recognition phase and (B) during test phase in controls, animals exposed during gestation and lactation (iAs-PND 15) and animals exposed during gestation, lactation and until PND 90 (iAs-PND 90). Each bar represents the mean ± SE (n = 8). Data were analyzed using an ANOVA. (*) Significantly different from controls after Dunnett’s post hoc test, P < 0.05. # P = 0.0625.
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Figure 6: The effect of As exposure on the spatial working memory in the recognition place task in male and female mice on PND 90. Discrimination index (DI) = (novel place exploration time/total exploration time). (A) male and female DI of location in the recognition phase and (B) during test phase in controls, animals exposed during gestation and lactation (iAs-PND 15) and animals exposed during gestation, lactation and until PND 90 (iAs-PND 90). Each bar represents the mean ± SE (n = 8). Data were analyzed using an ANOVA. (*) Significantly different from controls after Dunnett’s post hoc test, P < 0.05. # P = 0.0625.

Mentions: The place recognition task was used in 90 day old animals to determine if iAs exposure had an impact on the spatial memory, a function in which the hippocampal formation is strongly involved. The cognitive discrimination ability when an object changes location was evaluated in the different experimental groups of male and female mice including the control group, the iAs-PND 15 and iAs-PND 90 groups. During the recognition phase, no preference was observed for the location of the object or the object itself, which was measured as the time devoted to exploring each object (Figure 6A). In the test phase, iAs-PND 15 and iAs-PND 90 males showed significantly decreased recognition of the object location (Figure 6B). In contrast, this effect was marginally significant in iAs-PND 15 females and not significant in those with longer exposure (iAs-PND 90; Figure 6B).


Neurological effects of inorganic arsenic exposure: altered cysteine/glutamate transport, NMDA expression and spatial memory impairment.

Ramos-Chávez LA, Rendón-López CR, Zepeda A, Silva-Adaya D, Del Razo LM, Gonsebatt ME - Front Cell Neurosci (2015)

The effect of As exposure on the spatial working memory in the recognition place task in male and female mice on PND 90. Discrimination index (DI) = (novel place exploration time/total exploration time). (A) male and female DI of location in the recognition phase and (B) during test phase in controls, animals exposed during gestation and lactation (iAs-PND 15) and animals exposed during gestation, lactation and until PND 90 (iAs-PND 90). Each bar represents the mean ± SE (n = 8). Data were analyzed using an ANOVA. (*) Significantly different from controls after Dunnett’s post hoc test, P < 0.05. # P = 0.0625.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321597&req=5

Figure 6: The effect of As exposure on the spatial working memory in the recognition place task in male and female mice on PND 90. Discrimination index (DI) = (novel place exploration time/total exploration time). (A) male and female DI of location in the recognition phase and (B) during test phase in controls, animals exposed during gestation and lactation (iAs-PND 15) and animals exposed during gestation, lactation and until PND 90 (iAs-PND 90). Each bar represents the mean ± SE (n = 8). Data were analyzed using an ANOVA. (*) Significantly different from controls after Dunnett’s post hoc test, P < 0.05. # P = 0.0625.
Mentions: The place recognition task was used in 90 day old animals to determine if iAs exposure had an impact on the spatial memory, a function in which the hippocampal formation is strongly involved. The cognitive discrimination ability when an object changes location was evaluated in the different experimental groups of male and female mice including the control group, the iAs-PND 15 and iAs-PND 90 groups. During the recognition phase, no preference was observed for the location of the object or the object itself, which was measured as the time devoted to exploring each object (Figure 6A). In the test phase, iAs-PND 15 and iAs-PND 90 males showed significantly decreased recognition of the object location (Figure 6B). In contrast, this effect was marginally significant in iAs-PND 15 females and not significant in those with longer exposure (iAs-PND 90; Figure 6B).

Bottom Line: In humans, As species cross the placenta and are found in cord blood.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.Behavioral tasks showed significant spatial memory impairment in males while the effect was marginal in females.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México Mexico, DF, Mexico.

ABSTRACT
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 (CNS). 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.

No MeSH data available.


Related in: MedlinePlus