Effects of perfluorooctane sulfonate and its alternatives on long-term potentiation in the hippocampus CA1 region of adult rats in vivo

Abstract

With the limited but ongoing usage of perfluorooctane sulfonate (PFOS), the health effects of both PFOS and its alternatives are far from being understood. Long-term potentiation (LTP) was evaluated in rats after exposure to PFOS and its alternatives, aiming to provide some evidence about their potential to affect cognitive ability. Different dosages of PFOS and alternative chemicals, including perfluorohexane sulfonate (PFHxS), perfluorobutane sulfonate (PFBS) and chlorinated polyfluorinated ether sulfonate (Cl-PFAES), were given to rats via acute intracerebroventricular injection. The field excitatory postsynaptic potential (fEPSP) amplitude of the input/output functions, paired-pulse facilitations, and LTP in vivo were recorded. PFOS and its alternatives inhibited LTP in varying degrees, without significant effects on the normal synaptic transmission. In addition, PFHxS and Cl-PFAES exhibited comparable potential to PFOS in disturbing LTP. The results suggested that acute exposure to PFOS and its alternatives impaired the synaptic plasticity by a postsynaptic rather than a presynaptic mechanism. Besides, the fEPSP amplitude of the baseline was reduced by Cl-PFAES but not by other compounds, indicating that Cl-PFAES might act in a different mode. Providing some electrophysiological evidence and the potential mechanism of the neurotoxicity induced by PFOS and its alternatives, the present study addresses further evaluation of their safety and health risks.

Fig. 1. Effects of exposure to PFOS and its alternatives on LTP in the hippocampus CA1 region of rat. (A) Representative raw data traces before and after induction of LTP. The solid line is the fEPSP amplitude before HFS, and the dashed line is the fEPSP of LTP at 60 min after titanic stimulation. (B) The pooled data of standardized fEPSP amplitude monitored before and after HFS. Each point represents the mean fEPSP amplitude of three responses of stimuli. (C) Pooled results of LTP at 60 min after HFS. a/A, b/B, c/C, d/D indicate the difference with control, PFOS, PFHxS and PFBS groups, respectively. The lowercase letters indicate significant difference at p < 0.05 among control and the low dose group of four compounds. The capital letters indicate significant difference at p < 0.05 among control and the high dose group of four compounds. Asterisks indicate significant difference at p < 0.05 between the low and high dose groups of the same compound.

Fig. 2. Effects of Cl-PFAES at 10 μM and 100 μM on the baseline of fEPSP amplitude. (A) Basal fEPSP amplitude recordings 30 min before Cl-PFAES injection and 90 min after injection. Each point represents the mean fEPSP amplitude of three responses of stimuli. (B) The averaged fEPSP amplitude before and after injection of 10 μM and 100 μM Cl-PFAES. Pre-injection averaged the fEPSP amplitude in 30 min before injection, and post-injection averaged the fEPSP amplitude in 90 min after injection. *: p < 0.05, **: p < 0.01.

Fig. 3. Effects of exposure to PFOS and its alternatives in 10 μM and 100 μM on I/O curves and PPF in the hippocampus CA1 region in vivo. (A) I/O curves of fEPSP amplitude at varying stimulus current of 0.1–1.0 mA. (B) PPF of the fEPSP amplitude at varying ISIs of 10–400 ms.