Mechanisms of lead and manganese neurotoxicity.

Human exposure to neurotoxic metals is a global public health problem. Metals which cause neurological toxicity, such as lead (Pb) and manganese (Mn), are of particular concern due to the long-lasting and possibly irreversible nature of their effects. Pb exposure in childhood can result in cognitive and behavioural deficits in children.

Enhanced nitric oxide production during lead (Pb²⁺) exposure recovers protein expression but not presynaptic localization of synaptic proteins in developing hippocampal neurons.

We have previously reported that lead (Pb(2+)) exposure results in both presynaptic and postsynaptic changes in developing neurons as a result of inhibition of the N-methyl-d-aspartate receptor (NMDAR). NMDAR inhibition by Pb(2+) during synaptogenesis disrupts downstream trans-synaptic signaling of brain-derived neurotrophic factor (BDNF) and exogenous addition of BDNF can recover the effects of Pb(2+) on both presynaptic protein expression and presynaptic vesicular release. NMDAR activity can modulate other trans-synaptic signaling pathways, such as nitric oxide (NO) signaling.

Channelopathies: summary of the hot topic keynotes session.

The "Hot Topic Keynotes: Channelopathies" session of the 26th International Neurotoxicology Conference brought together toxicologists studying interactions of environmental toxicants with ion channels, to review the state of the science of channelopathies and to discuss the potential for interactions between environmental exposures and channelopathies. This session presented an overview of chemicals altering ion channel function and background about different channelopathy models. It then explored the available evidence that individuals with channelopathies may or may not be more sensitive to effects of chemicals.

Lead exposure during synaptogenesis alters NMDA receptor targeting via NMDA receptor inhibition.

N-methyl-D-aspartate receptor (NMDAR) ontogeny and subunit expression are altered during developmental lead (Pb²+) exposure. However, it is unknown whether these changes occur at the synaptic or cellular level. Synaptic and extra-synaptic NMDARs have distinct cellular roles, thus, the effects of Pb²+ on NMDAR synaptic targeting may affect neuronal function.

Molecular neurobiology of lead (Pb(2+)): effects on synaptic function.

Lead (Pb(2+)) is a ubiquitous environmental neurotoxicant that continues to threaten public health on a global scale. Epidemiological studies have demonstrated detrimental effects of Pb(2+) on childhood IQ at very low levels of exposure. Recently, a mechanistic understanding of how Pb(2+) affects brain development has begun to emerge.

Allethrin differentially modulates voltage-gated calcium channel subtypes in rat PC12 cells.

Pyrethroid insecticides are one of the most widely used classes of insecticides. Previous studies revealed that pyrethroids potently affect the insect voltage-gated sodium (Na(+)) channel (VGSC), resulting in prolonged channel open time. However, recent findings have suggested that pyrethroids may affect targets other than the VGSC.

Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling.

Lead (Pb(2+)) exposure is known to affect presynaptic neurotransmitter release in both in vivo and cell culture models. However, the precise mechanism by which Pb(2+) impairs neurotransmitter release remains unknown. In the current study, we show that Pb(2+) exposure during synaptogenesis in cultured hippocampal neurons produces the loss of synaptophysin (Syn) and synaptobrevin (Syb), two proteins involved in vesicular release.