Developmental Perfluorooctanesulfonic acid (PFOS) exposure as a potential risk factor for late-onset Alzheimer’s disease in CD-1 mice and SH-SY5Y cells

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants

“…A recent study found an increased expression of two Alzheimer's disease biomarkers, APP and Tau proteins. Phosphorylation of Tau (on ser-404 and thr-181) also increases as well as Taurelated kinase GSK3ꞵ levels upon treatment with low doses of PFOS (0.001 µM during 24h) suggesting a potential implication of PFOS on Alzheimer's pathogenic pathways [190].…”

“…Exposure of undifferentiated and RA-differentiated SH-SY5Y cells to PFOS also causes a concentration-and time-dependent decrease in cell viability [190][191][192][193][194][195][196], and an increase in apoptotic cell death, which may be due to PFOS-induced oxidative stress [191][192][193][194][195][196] (Supplementary Table 4). Indeed, exposure to PFOS increases ROS and lipid peroxidation, and decreases the antioxidant enzyme activity GPx, leading to cell apoptosis [191,195,196].…”

“…Associated references 20 µM RA for 4 days [63] 10 µM RA for 6 days, starting at 80% confluence [190] 20 µM RA for 4 days [185] 20 µM RA for 4 days, starting at 60-80% confluence [64,65] 10 µM RA for 4 days, starting at 60-80% confluence [66] 10 µM RA for 3 days or 100 ng/mL NGF for 2 days, starting at 60-80% confluence [58] 10 µM RA for 7 days [59] 10 µM RA for 5 days, starting 24h after seeding [59][60][61] 1 µM RA for 72 h, starting 24h after seeding [51][52][53] 7 ng/mL NGF for up to 12 days, starting 24h after seeding [57] 10 µM RA for 5 days followed by 50 mg/mL BDNF during 5 days [30] 10 µM RA for 2 or 3 days [159] 1 µM RA for 3 days, starting 24h after seeding [134] 1 µg/mL NGF for 5 days [110] 1 µg/mL NGF for 5-7 days [111] 10 µM RA for 2 days, starting at 70-80% confluence [105] 10 µM RA for 7 days, starting 24h after seeding [62] 3 µM RA for 1 day or 10 µM RA for 4 or 8 days [87] 10 µM RA for 6 days, starting 24h after seeding [151,189] J o u r n a l P r e -p r o o f 59 20 µM RA for 65 days, starting 4 days after seeding [74] 10 µM RA for 6 days followed of 10 µM RA, 50 ng/mL BDNF, 1x B-27 and 200 µM dbcAMP for 8 more days [56] Declaration of interests ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:…”

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes

“…There is growing evidence that PFOS, PFOA, and PFAS mixtures lead to changes in neurotransmitter levels, ,− alter neurotransmitter receptor and transporter expression and function, ,,,,,− and change neurotransmitter metabolism. ,− ,,,,,,,,,, Although the major focus for the evaluation of PFAS neurotoxicity has been on PFAS developmental neurotoxicity, ,,,− ,− ,,,,,,,,− PFAS exposure during both development and adulthood may change neurotransmitter levels in a brain region-specific manner (Table ). Lifelong exposure of humans to PFAS may result in dynamic changes in neurological function resulting from PFAS accumulation over time.…”

“…Rats developmentally exposed to PFOS increased Tau phosphorylation and protein expression as well as amyloid precursor protein (APP) and amyloid-β 1–42 (Aβ1–42) in adults, , suggesting that the developmental exposure to PFOS may be involved in the development of neurodegenerative diseases, particularly Alzheimer’s disease (AD) later in life. Another study determined that rats exposed to PFOS increased hippocampal protein levels of total Tau, phospho-Tau-S199, and amyloid-β (Aβ) as well as increased the amount of amyloid precursor protein (APP) mRNA .…”