Changes in Synaptic Transmission, Calcium Current, and Neurite Growth by Perfluorinated Compounds Are Dependent on the Chain Length and Functional Group

Abstract

Scientific and public concerns on perfluorinated compounds (PFCs) are increasingly growing because of their environmental persistency, bioaccumulation, and extensive distribution throughout the world. Little is known about the effects of PFCs on neural function and the underlying mechanisms. Recent evidence suggests that the toxicological effects of PFCs are closely correlated with their carbon chain lengths. In this present work, the actions of PFCs with varying chain length on cultured rat hippocampal neurons and possible action patterns were examined. Increases in the frequencies of spontaneous miniature postsynaptic current (mPSC) were commonly found in cultured neurons when perfused with PFCs. The increase of mPSC frequency was in proportion to the carbon chain length, and the potency of perfluorinated carboxylates was less pronounced than that of perfluorinated sulfonates. A comparable but less perceptible trend was also found for the amplitudes of voltage-dependent calcium current (I Ca ). No regular change in pattern was observed for the effects of PFCs on activation and inactivation kinetics of I Ca . Furthermore, prolonged treatment of PFCs inhibited the neurite growth of neurons to various degrees. Comparisons between nonfluorinated and perfluorinated analogues demonstrated that the fluorination in alkyl chain exerts stronger actions on neurons as compared to the surfactant activity. This study shows that PFCs exhibit adverse effects on cultured neurons to various extents, which is dependent on the carbon chain length and functional group attached to the fully fluorinated alkyl chain.

Differential toxicity between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA)

“…Because the acute oral convulsive dose of PFOS was 250 mg/kg , the convulsion induced by PFOS seemed to depend on its total dose regardless of treatment schedule. The information provided by Liao et al (2009), that the potency on increases in the frequencies of spontaneous mPSC of perfluorinated carboxylates was less pronounced than that of perfluorinated sulfonates, is supportive to this PFOS-specific neurotoxicity. Kawamoto et al (2008) reported as follows: PFOS (15 μM or higher) but not PFOA caused backward swimming of paramecia, which was induced by intracellular free Ca2 + at 0.2 μM and higher.…”

“…PFOS induced cell membrane excitability, and the action potential of the paramecium was induced at lower current intensity with PFOS. The ultrasonic-induced fatal tonic convulsion of rodents might be related to the PFOS-specific cell membrane excitability shown by Liao et al (2009) and Kawamoto et al (2008).…”

“…Effects observed included altered levels of excitatory amino acids in the brain of rats (Yang et al, 2009), and changes in neurotransmitter levels and increases in miniature post-synaptic currents (mPSC) along with inward calcium currents shown in cultured Sprague-Dawley rat hippocampal neurons (Liao et al, 2009). One study by using the Morris water maze found effects on learning and memory in mice at approximately 2 mg/kg/day (Long et al, 2013).…”

“…The in vivo observations were supported by changes in the expression of a variety of neurologically active brain proteins in the treated pups. The results of an in vitro study of hippocampal synaptic transmission and neurite growth showed that 50 and 100 μM PFOA increased spontaneous synaptic current and had an equivocal impact on neurite growth (Liao et al, 2009). fatal tonic convulsions appeared in the PFOS-treated rats (250 mg/kg or more) and mice (125 mg/kg or more) when ultrasonic stimulus was applied to the animals.…”

Polar Stir Bars for Isolation and Preconcentration of Perfluoroalkyl Substances from Human Milk Samples Prior to UHPLC–MS/MS Analysis

“…Potential health effects in animal models have been reported by several authors [8]. PFASs are also considered endocrine disrupting chemicals (EDCs), with a particular debate related to their possible impact on reproductive functions in man [9][10][11]. PFOA and PFOS have been linked to disorders in homeostatic sexuality hormones and have been associated with the increase of fetal resorptions and abortions in animals.…”