Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
1597313
Reference Type
Journal Article
Title
Effects of sodium arsenite on neurite outgrowth and glutamate AMPA receptor expression in mouse cortical neurons
Author(s)
Maekawa, F; Tsuboi, T; Oya, M; Aung, KH; Tsukahara, S; Pellerin, L; Nohara, K
Year
2013
Is Peer Reviewed?
1
Journal
NeuroToxicology
ISSN:
0161-813X
EISSN:
1872-9711
Publisher
Elsevier
Volume
37
Issue
Elsevier
Page Numbers
197-206
Language
English
PMID
23694735
DOI
10.1016/j.neuro.2013.05.006
Web of Science Id
WOS:000321413400024
URL
https://linkinghub.elsevier.com/retrieve/pii/S0161813X13000831
Exit
Abstract
There has been broad concern that arsenic in the environment exerts neurotoxicity. To determine the mechanism by which arsenic disrupts neuronal development, primary cultured neurons obtained from the cerebral cortex of mouse embryos were exposed to sodium arsenite (NaAsO2) at concentrations between 0 and 2μM from days 2 to 4 in vitro and cell survival, neurite outgrowth and expression of glutamate AMPA receptor subunits were assessed at day 4 in vitro. Cell survival was significantly decreased by exposure to 2μM NaAsO2, whereas 0.5μM NaAsO2 increased cell survival instead. The assessment of neurite outgrowth showed that total neurite length was significantly suppressed by 1μM and 2μM NaAsO2, indicating that the lower concentration of NaAsO2 impairs neuritogenesis before inducing cell death. Immunoblot analysis of AMPA receptor subunit expression showed that the protein level of GluA1, a specific subunit of the AMPA receptor, was significantly decreased by 1μM and 2μM NaAsO2. When immunocytochemistry was used to confirm this effect by staining for GluA1 expression in neuropeptide Y neurons, most of which contain GluA1, GluA1 expression in neuropeptide Y neurons was found to be significantly suppressed by 1μM and 2μM NaAsO2 but to be increased at the concentration of 0.5μM. Finally, to determine whether neurons could be rescued from the NaAsO2-induced impairment of neuritogenesis by compensatory overexpression of GluA1, we used primary cultures of neurons transfected with a plasmid vector to overexpress either GluA1 or GluA2, and the results showed that GluA1/2 overexpression protected against the deleterious effects of NaAsO2 on neurite outgrowth. These results suggest that the NaAsO2 concentration inducing neurite suppression is lower than the concentration that induces cell death and is the same as the concentration that suppresses GluA1 expression. Consequently, the suppression of GluA1 expression by NaAsO2 seems at least partly responsible for neurite suppression induced by NaAsO2.
Keywords
Arsenic; Neuron; Neurite; Glutamate; GluA1; GluA2
Tags
IRIS
•
Arsenic Hazard ID
PubMed
Considered New
PubMed
Considered New
PubMed
ToxNet
Considered New
WOS
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
2. Lit Search Updates through Oct 2015
PubMed
WOS
ToxNet
Considered
7. Other Studies through Oct 2015
MOA
•
Arsenic (Inorganic)
1. Literature
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
4. Adverse Outcome Pathways/Networks Screening
Relevant
•
Arsenic MOA
4. Adverse Outcome Pathways
Other MOA
1. MOA Literature Screening
Health Effect Screening
•
Arsenic Susceptibility
Life Stages Citation Mapping
15%-20%
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity