Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptorsReport as inadecuate




Mercury-induced toxicity of rat cortical neurons is mediated through N-methyl-D-Aspartate receptors - Download this document for free, or read online. Document in PDF available to download.

Molecular Brain

, 5:30

First Online: 14 September 2012Received: 13 August 2012Accepted: 11 September 2012

Abstract

BackgroundMercury 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.

ResultsWe 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 Cai. The observed increases in neuronal activity and Cai 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.

ConclusionsCollectively, our data show that HgCl2-induced toxic effects on central neurons are triggered by an over-activation of NMDA receptors, leading to cytoskeleton instability.

KeywordsMercury Chloride Rat cortical neurons Toxicity MK 801 NMDA receptor Excitotoxicity Cytoskeleton Electronic supplementary materialThe online version of this article doi:10.1186-1756-6606-5-30 contains supplementary material, which is available to authorized users.

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Author: Fenglian Xu - Svetlana Farkas - Simone Kortbeek - Fang-Xiong Zhang - Lina Chen - Gerald W Zamponi - Naweed I Syed

Source: https://link.springer.com/







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