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Mercury compounds disrupt neuronal glutamate transport in cultured mouse cerebellar granule cells
Author(s) -
Fonfría Elena,
Vilaró M. Teresa,
Babot Zoila,
RodríguezFarré Eduard,
Suñol Cristina
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20375
Subject(s) - glutamate receptor , chemistry , neurotoxicity , glutamate aspartate transporter , glutamic acid , biochemistry , extracellular , cerebellum , microbiology and biotechnology , biophysics , biology , metabotropic glutamate receptor , amino acid , toxicity , neuroscience , receptor , organic chemistry
Abstract Cerebellar 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′‐diisothiocyanato‐stilbene‐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.