Zinc changes evoked by phenolic compounds and effect on TEA-LTP at hippocampal mossy fiber synapses

Abstract

The analysis of phenolic compounds pollution on health is a topic of major concern, in particular the effects associated with cellular damages. In central nervous system synapses zinc can be either a neuromodulator or a neurotoxin, depending on the intracellular concentration and may be implicated in various neurodegenerative diseases. The way phenolic compounds affect synaptic zinc thus contributes to the protective or toxic neuronal zinc changes that can be detected by means of fluorescent zinc indicators. This work focused on the influence of phenolic pollutants on postsynaptic zinc changes, including during chemically induced long term potentiation (LTP). The study was performed in hippocampal slices (400 μm), at the mossy fiber - CA3 pyramidal cells synaptic system, containing, in the synaptic vesicles, very high concentrations of loosely bound zinc. The slices, obtained from pregnant (16-18 days) Wistar rats (12-16 weeks old), were incubated during 1 h, in an oxygenated artificial cerebrospinal fluid (ACSF) containing 5 μM of the permeant fluorescent zinc probe Newport Green (Kd = 1 μM). The effect of a mixture of six phenolic pollutants (100 mg/L each) on the zinc signals was a reversible enhancement (35%, n = 2) indicating that those compounds activate intense zinc release followed by zinc entry in the postsynaptic area. The action of the compounds was also evaluated on the zinc changes associated with TEA-LTP, evoked subsequently by an ACSF solution containing TEA (25 mM) and high calcium (10 mM). It was found that the zinc signals measured in the modified ACFS, applied after the pollutants, have a similar behavior to that observed in control experiments, i.e. the signals decrease in a reversible way (to about 75 % of baseline, n = 3). This reduction, which may be due to the activation of presynaptic Katp channels, was observed both in the absence and following the application of the mixture of compounds, suggesting that mossy fiber TEA-LTP is not largely affected by the pollutants.