Arsenite exposure altered the expression of NMDA receptor and postsynaptic signaling proteins in rat hippocampus
Abstract
Chronic arsenic exposure has an adverse effect on neurobehavioral function. Our previous study demonstrated an elevated arsenic level, ultra-structure changes and reduced NR2A gene expression in hippocampus, and impaired spatial learning in arsenite-exposed rats. The NMDA receptor and the postsynaptic signaling proteins CaMKII, postsynaptic density protein 95 (PSD-95), synaptic Ras GTPase-activating protein (SynGAP) and nuclear activated extracellular-signal regulated kinase (ERK1/2) play important roles in synaptic plasticity, learning and memory. We hypothesized that the above molecular expression changes may contribute to arsenic neurotoxicity. In present study, the expression of NMDA receptor and postsynaptic signaling proteins in hippocampus were evaluated in rats exposed to 0, 2.72, 13.6 and 68 mg/L sodium arsenite for 3 months. Decreased protein expression of NR2A, PSD-95 and p-CaMKII α in the hippocampus of arsenite-exposed rats was observed, while the expression of SynGAP, a negative regulator of Ras-MAPK activity, was increased when compared with the controls. Additionally, decreased p-ERK1/2 activity was found in the hippocampus of arsenite-exposed rats. These data suggest that altered expression of NMDA receptor complex and postsynaptic signaling proteins may explain arsenic-induced neurotoxicity.
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Arsenic impairs glutamatergic signaling by reducing expression of the NR2A subunit of the NMDA receptor in the hippocampus, a change associated with impaired LTP and deficits in learning and memory.
“Arsenic impairs glutamatergic signaling by reducing expression of the NR2A subunit of the NMDA receptor in the hippocampus, a change associated with impaired LTP and deficits in learning and memory (Luo et al., 2012, 2009; Zsarnovszky et al., 2024).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Luo et al., 2012
Cites
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Interaction with the NMDA receptor locks CaMKII in an active conformation
Bayer, K.-U., De Koninck, P., Leonard, A. S., Hell, J. W., & Schulman, H. (2001) · Nature · doi:10.1038/35081080 · Cited by 732 · see citing works
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SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
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Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
“Arsenic impairs glutamatergic signaling by reducing expression of the NR2A subunit of the NMDA receptor in the hippocampus, a change associated with impaired LTP and deficits in learning and memory (Luo et al., 2012, 2009; Zsarnovszky et al., 2024).”
- Authors
- Luo, J.-H., Qiu, Z.-Q., Zhang, L., & Shu, W.-Q.
- Affiliations
- Army Medical University (CN)
- ORCID
- Zhang, Liang
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 211
- Issue
- 1
- Pages
- 39-44
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W2069704122
- Cited by
- 71
- References
- 4
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 1 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30800921)
- Natural Science Foundation of Chongqing (2008BB7115)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- arsenic neurotoxicity, arsenite, NMDA receptor, NR2A, hippocampus, postsynaptic signaling, PSD-95, CaMKII, SynGAP, ERK1/2, synaptic plasticity
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Dose-Response Relationship, Drug, Hippocampus, Male, Membrane Proteins, Blotting, Western, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Arsenites, GTPase-Activating Proteins, Intracellular Signaling Peptides and Proteins, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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