Clioquinol and vitamin B12 (cobalamin) synergistically rescue the lead-induced impairments of synaptic plasticity in hippocampal dentate gyrus area of the anesthetized rats in vivo.

Lead (Pb(2+)) exposure in development induces impairments of synaptic plasticity in the hippocampal dentate gyrus (DG) area of the anesthetized rats in vivo. The common chelating agents have many adverse effects and are incapable of alleviating lead-induced neurotoxicity. Recently, CQ, clioquinol (5-chloro-7-iodo-8-hydroxy-quinoline), which is a transition metal ion chelator and/or ionophore with low affinity for metal ions, has yielded some promising results in animal models and clinical trials related to dysfunctions of metal ions. In addition, CQ-associated side effects are believed to be overcome with vitamin B12 (VB12) supplementation. To determine whether CQ treatment could rescue impairments of synaptic plasticity induced by chronic Pb(2+) exposure, we investigated the input/output functions (I/Os), paired-pulse reactions (PPRs) and long-term potentiation (LTP) of different treatment groups in hippocampal DG area of the anesthetized rat in vivo by recording field potentials and measured hippocampal Pb(2+) concentrations of different treatment groups by PlasmaQuad 3 inductive coupled plasma mass spectroscopy. The results show: CQ alone does not rescue the lead-induced impairments of synaptic plasticity in hippocampal DG area of the anesthetized rats in vivo; VB12 alone partly rescues the lead-induced impairments of LTP; however the co-administration of CQ and VB12 totally rescues these impairments of synaptic plasticity and moreover, the effects of CQ and VB12 co-administration are specific to the lead-exposed animals.

Lead inhibited N-methyl-D-aspartate receptor-independent long-term potentiation involved ryanodine-sensitive calcium stores in rat hippocampal area CA1.

Lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term potentiation (LTP) has been reported in area CA1 of rat hippocampus following lead exposure in vivo and in vitro. The present study was carried out to investigate whether the alterations of N-methyl-d-aspartate (NMDA) receptor-independent LTP following lead exposure involve internal calcium stores in hippocampus CA1 synapses. Monosynaptic field excitatory postsynaptic potentials in hippocampal slice area CA1 were recorded using the whole-cell patch-clamp upon acute lead treatment, and these studies were coupled with calcium imaging experiments to observe internal calcium changes in cultured hippocampal neurons. Inhibiting calcium release by ryanodine significantly reduced NMDA receptor-independent LTP, and depletion of internal calcium stores with thapsigargin blocked this form of LTP. Caffeine, an agonist of ryanodine receptors, enhanced this form of LTP. However, caffeine-enhanced NMDA receptor-independent LTP was depressed after bath application of lead. Moreover, lead further decreased ryanodine- and thapsigargin-reduced NMDA receptor-independent LTP. Calcium imaging also confirmed that lead had an effect on internal calcium release and uptake. Taken together, these results demonstrated that lead inhibited NMDA receptor-independent LTP by action on calcium release and uptake by ryanodine-sensitive stores in rat hippocampal area CA1.

Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo.

Previous studies have demonstrated that synaptic plasticity, which includes long-term potentiation (LTP) and depotentiation (DP) in hippocampus, is important for learning and memory. The purpose of this study is to evaluate the effect of taurine via drinking water on the lead-induced impairments of LTP and DP in rat dentate gyrus (DG) in vivo. The experiments were carried out in four groups of rats (control, lead-exposed, control and lead-exposed with a taurine-supplement diet, respectively). The input-output (I/O) function, excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG area of adult rats (60-90 days) in response to stimulation applied to the lateral perforant path. The results show that: 1. chronic lead exposure impaired LTP/DP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; 2. in control rats, taurine had no effect on LTP/DP; 3. the amplitudes of LTP/DP of lead-exposed group were significantly increased by applying taurine. These results suggest that dietary taurine supplement could protect rats from the lead-induced impairments of synaptic plasticity and might be a preventive medicine to cure the cognitive deficits induced by lead.

Effects of chronic lead exposure on 1H MRS of hippocampus and frontal lobes in children.

The authors performed IQ testing and magnetic resonance spectroscopy on six lead-exposed and six control children. Levels of N-acetyl aspartate (neuronal density and mitochondrial metabolism), creatine + phosphocreatine (phosphate metabolism), and choline (membrane turnover) were decreased in four brain regions (left and right frontal, left and right hippocampus) in lead-exposed children vs controls. The reductions were right frontal > left frontal > hippocampus but were the same bilaterally in the hippocampus.