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Mercury compounds disrupt neuronal glutamate transport in cultured mouse cerebellar granule cells

AuthorsFonfría, Elena; Vilaró, Maria Teresa ; Babot, Zoila ; Rodríguez-Farré, Eduard; Suñol, Cristina
KeywordsGlutamate release
Mechanisms of neurotoxicity
Cultured neurons
Mercuric chloride
[3H]aspartate uptake
Issue Date15-Feb-2005
PublisherJohn Wiley & Sons
CitationJournal of Neuroscience Research 79(4): 545-553 (2005)
AbstractCerebellar granule cells are targeted selectively by mercury compounds in vivo. Despite the affinity of mercury for thiol groups present in all cells, the molecular determinant(s) of selective cerebellar degeneration remain to be elucidated fully. We studied the effect of mercury compounds on neuronal glutamate transport in primary cultures of mouse cerebellar granule cells. Immunoblots probed with an antibody against the excitatory amino acid transporter (EAAT) neuronal glutamate transporter, EAAT3, revealed the presence of a specific band in control and mercury-treated cultures. Micromolar concentrations of both methylmercury and mercuric chloride increased the release of endogenous glutamate, inhibited glutamate uptake, reduced mitochondrial activity, and decreased ATP levels. All these effects were completely prevented by the nonpermeant reducing agent Tris-(2-carboxyethyl)phosphine (TCEP). Reduction of mitochondrial activity by mercuric chloride, but not by methylmercury, was inhibited significantly by 4,4′- diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) and by reduced extracellular Cl- ion concentration. In addition, DIDS and low extracellular Cl- completely inhibited the release of glutamate induced by mercuric chloride, and produced a partial although significant reduction of that induced by methylmercury. We suggest that a direct inhibition of glutamate uptake triggers an imbalance in cell homeostasis, leading to neuronal failure and Cl--regulated cellular glutamate efflux. Our results demonstrate that neuronal glutamate transport is a novel target to be taken into account when assessing mercury-induced neurotoxicity. ©2005 Wiley-Liss, Inc.
Publisher version (URL)http://dx.doi.org/10.1002/jnr.20375
Identifiersdoi: 10.1002/jnr.20375
issn: 0360-4012
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