Developmental perfluorooctane sulfonate exposure inhibits long-term potentiation by affecting AMPA receptor trafficking.

Affiliation

Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Dalian, 116024, Liaoning, China. Electronic address: [Email]

Abstract

Both animal study and epidemiological survey revealed the associations between defects of cognitive function and the developmental exposure to perfluorooctane sulfonate (PFOS), while the mechanism is not well known. The SD rats were exposed PFOS at 1.7, 5 and 15 mg/L by drinking water from gestation to the adulthood of the pups for evaluating the effects of PFOS exposure on long-term potentiation (LTP) and the role of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors trafficking. Whole-life exposure of PFOS beginning in utero to adulthood significantly inhibited the induction and expression of LTP, and the input/output curve (I/O) and paired-pulse facilitation (PPF) were moderately suppressed, suggesting that PFOS might affect the synaptic transmission and plasticity both in pre- and post-synaptic cells. Meanwhile, PFOS decreased the mRNA levels of AMPA receptor subunits GluA1 and GluA2, and the protein amounts in the membrane, with the total GluA1 and GluA2 protein amounts increased, indicating the internalization of AMPA receptors. Furthermore, tests in the primary hippocampal neurons also support the decreased mRNA levels of GluA1 and GluA2 induced by PFOS. After the pretreatment of AMPA antagonist (NBQX), PFOS decreased the expression of GluA1 and GluA2 and increased internal cellular calcium at much lower levels than that in the neurons without NBQX treatment. The results provide electrophysiological evidence for the impaired cognitive function induced by PFOS exposure and revealed the critical role of AMPA receptor involved.

Keywords

AMPA,Ca(2+),LTP,Learning and memory,PFOS,