title: 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.
authors.affiliation: Department of Environmental Hygiene, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Jiao-hua
authors.initials: JH
authors.lastname: Luo
authors.forename: Zhi-qun
authors.initials: ZQ
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Wei-qun
authors.initials: WQ
authors.lastname: Shu
mesh_terms: D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000096:biosynthesis / Q000187:drug effects; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D020690:GTPase-Activating Proteins / Q000096:biosynthesis / Q000187:drug effects; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D018053:Arsenites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C501449:Dlg4 protein, rat; C112202:Syngap1 protein, rat; C015001:arsenite