Chronic Exposure to Perfluorooctane Sulfonate Induces Behavior Defects and Neurotoxicity through Oxidative Damages, In Vivo and In Vitro

Abstract

Perfluorooctane sulfonate (PFOS) is an emerging persistent pollutant which shows multiple adverse health effects. However, the neurotoxicity of PFOS and its mechanisms have not been fully elucidated. Using a combination of in vivo and in vitro methods, the present study provides a detailed description of PFOS-induced neurotoxicity. Results showed that the median lethal concentration of PFOS was 2.03 mM in Caenorhabditis elegans for 48 h exposure. 20 µM PFOS caused decrease of locomotor behaviors including forward movement, body bend and head thrash. Additionally, PFOS exposure reduced chemotaxis index of C. elegans, which indicates the decline of chemotaxis learning ability. Using green fluorescent protein (GFP) labelled transgenic strains, we found that PFOS caused down-regulated expression of a chemoreceptor gene, gcy-5, in ASE chemosensory neurons, but did not affect cholinergic neurons and dopaminergic neurons. In SH-SY5Y cells, 48 h exposure to 25 µM and 50 µM PFOS induced cell damage, apoptosis and the reactive oxygen species (ROS) generation. PFOS caused significant increases of lipid peroxidation and superoxide dismutase activity, but an actual decrease of glutathione peroxidase activity. Furthermore, antioxidant N-acetylcysteine rescued cells from PFOS-induced apoptosis via blocking ROS. Our results demonstrate that chronic exposure to PFOS can cause obvious neurotoxicity and behavior defects. Oxidative damage and anti-oxidative deficit are crucial mechanisms in neurotoxicity of PFOS.

Chronic Exposure to Perfluorooctane Sulfonate Reduces Lifespan of Caenorhabditis elegans Through Insulin/IGF-1 Signaling

“…Multiple toxic effects of PFOS have been demonstrated in previous studies (Lau et al 2007;Ahrens and Bundschuh 2014;Chen et al 2014). For the first time, our results revealed that chronic exposure to PFOS affected longevity of animals.…”

“…Age-synchronized nematodes were produced for experiments by collecting adult nematodes into tubes by washing plates with M9 buffer, and then dissolving the adults using a bleach-containing buffer (0.45 N NaOH, 2 % HClO) to release eggs. The eggs were collected and hatched on the plates without food, then synchronized for experiments (Chen et al 2014).…”

“…Pharmacokinetic studies determined that the elimination half-life of PFOS was more than 90 days in rats, and about 5.4 years in humans (Mariussen 2012). Multiple adverse effects of PFOS have been found, including developmental toxicity, endocrine disruption, immunotoxicity and neurotoxicity (Lau et al 2007;Ahrens and Bundschuh 2014;Chen et al 2014). However, little is known about whether chronic exposure to PFOS can accelerate aging and affect animal longevity.…”

Temperature-dependent effects of PFOS on risk recognition and fast-start performance in juvenile Spinibarbus sinensis

“…Johansson et al (2008Johansson et al ( , 2009) speculated that PFOS exposure could affect processes linked to neurodegeneration, thereby af fecting cognitive function. Chen et al (2014) re ported that in Caenorhabditis elegans, PFOS induced ob vious behavioral defects (e.g. the decline of chemo taxis learning ability) and neurotoxicity via oxidative stress damages.…”

“…Most toxicological tests concerning PFOS in fish have focused on metabolic, reproductive and developmental aspects (Hagenaars et al 2008, Han & Fang 2010, Dorts et al 2011. However, there is limited but growing evidence linking PFOS exposure to the toxic contamination of the central nervous system (Austin et al 2003, Johansson et al 2009, Chen et al 2014. As reported by Johansson et al (2009), PFOS exposure can affect processes linked to neurodegeneration, thereby affecting cognitive function.…”