Organic solvent-induced changes in membrane geometry in human SH-SY5Y neuroblastoma cells - a common narcotic effect?

Exposure to organic solvents may cause narcotic effects. At the cellular level, these narcotic effects have been associated with a reduction in neuronal excitability caused by changes in membrane structure and function. In order to critically test whether changes in membrane geometry contribute to these narcotic effects, cultured human SH-SY5Y neuroblastoma cells have been exposed to selected organic solvents.

Sense in Pb2+ sensing.

It is generally acknowledged that Pb(2+), which is sequestered by live cells from their direct environment, affects a large number of cellular processes at picomolar to micromolar concentrations. However, resolving the specific molecular targets and mechanisms responsible for the neurotoxic effects of this xenobiotic metal is hampered by the lack of suitable tools to investigate the intracellular dynamics of Pb(2+) at low concentrations. Fluorescent Ca(2+) indicators have been used as Pb(2+) sensors and have proven useful to detect cellular Pb(2+) entry and to estimate the overall intracellular free Pb(2+) concentration associated with adverse cellular effects.

Selective inhibition of human heteromeric alpha9alpha10 nicotinic acetylcholine receptors at a low agonist concentration by low concentrations of ototoxic organic solvents.

Ethylbenzene and para-xylene (p-xylene), but not the chemically closely related organic solvents ortho-xylene (o-xylene) and meta-xylene (m-xylene), are known to cause ototoxicity and irreversible hearing loss, though the underlying mechanisms are still unknown. In this study, effects of ethylbenzene and of p-, o-, and m-xylene on human heteromeric alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated using the two-electrode voltage clamp technique. ACh dose-dependently evoked an alpha9alpha10 nAChR-mediated ion current with an EC(50) of 137 microM.

Hydroxylation increases the neurotoxic potential of BDE-47 to affect exocytosis and calcium homeostasis in PC12 cells.

Background: Oxidative metabolism, resulting in the formation of hydroxylated polybrominated diphenyl ether (PBDE) metabolites, may enhance the neurotoxic potential of brominated flame retardants.

Objective: Our objective was to investigate the effects of a hydroxylated metabolite of 2,2',4,4'-tetra-bromodiphenyl ether (BDE-47; 6-OH-BDE-47) on changes in the intracellular Ca2+ concentration ([Ca2+]i) and vesicular catecholamine release in PC12 cells.

Methods: We measured vesicular catecholamine release and [Ca2+]i using amperometry and imaging of the fluorescent Ca2+-sensitive dye Fura-2, respectively.

Neonatal exposure to brominated flame retardant BDE-47 reduces long-term potentiation and postsynaptic protein levels in mouse hippocampus.

Background: Increasing environmental levels of brominated flame retardants raise concern about possible adverse effects, particularly through early developmental exposure.

Objective: The objective of this research was to investigate neurodevelopmental mechanisms underlying previously observed behavioral impairments observed after neonatal exposure to polybrominated diphenyl ethers (PBDEs).

Methods: C57Bl/6 mice received a single oral dose of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on postnatal day (PND) 10 (i.