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  • Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D-Aspartate receptors.

Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D-Aspartate receptors.

Molecular brain (2012-09-18)
Fenglian Xu, Svetlana Farkas, Simone Kortbeek, Fang-Xiong Zhang, Lina Chen, Gerald W Zamponi, Naweed I Syed
ABSTRACT

Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer's disease, Parkinson's disease, epilepsy, depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid) on cultured, rat cortical neurons. We found that inorganic mercuric chloride (HgCl₂--at 0.025 to 25 μM) not only caused neuronal degeneration but also perturbed neuronal excitability. Whole-cell patch-clamp recordings of pyramidal neurons revealed that HgCl₂ not only enhanced the amplitude and frequency of synaptic, inward currents, but also increased spontaneous synaptic potentials followed by sustained membrane depolarization. HgCl₂ also triggered sustained, 2-5 fold rises in intracellular calcium concentration ([Ca²⁺]i). The observed increases in neuronal activity and [Ca²⁺]i were substantially reduced by the application of MK 801, a non-competitive antagonist of N-Methyl-D-Aspartate (NMDA) receptors. Importantly, our study further shows that a pre incubation or co-application of MK 801 prevents HgCl₂-induced reduction of cell viability and a disruption of β-tubulin. Collectively, our data show that HgCl₂-induced toxic effects on central neurons are triggered by an over-activation of NMDA receptors, leading to cytoskeleton instability.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mercury standard solution, suitable for atomic absorption spectrometry, 1 mg/mL Hg, 1000 ppm Hg
Sigma-Aldrich
Mercury(II) chloride, ≥98%
Sigma-Aldrich
Mercury(II) chloride, ReagentPlus®, 99%
Sigma-Aldrich
Mercury(II) chloride, ACS reagent, ≥99.5%