Effects of perfluorooctane sulfonate (PFOS) on cognitive behavior and autophagy of male mice

J Toxicol Sci. 2023;48(9):513-526. doi: 10.2131/jts.48.513.

Abstract

Perfluorooctane sulfonate (PFOS), an emerging environmental pollutant, is reported to cause neurotoxicity in animals and humans, but its underlying mechanisms are still unclear. We used in vivo models to investigate the effects of PFOS on cognition-related behaviors and related mechanisms. After 45 days of intragastric administration of PFOS (2 mg/kg or 8 mg/kg) in 7-week-old C57BL/6 mice, muscle strength, cognitive function and anxiety-like behavior were evaluated by a series of behavioral tests. The underling mechanisms of PFOS on impaired behaviors were evaluated by HE/Nissl staining, electron microscopy observation and western blot analysis. The results indicated that PFOS-exposed mice exhibited significant cognitive impairment, anxiety, neuronal degeneration and the abnormities of synaptic ultrastructure in the cortex and hippocampus. Western blot analysis indicated that PFOS exposure increased microtubule-associated protein light chain 3 (LC3) and decreased p62 protein levels, which may be associated with activation of autophagy leading to neuron damage. In summary, our results suggest that chronic exposure to PFOS adversely affects cognitive-related behavior in mice. These findings provide new mechanistic insights into PFOS-induced neurotoxicity.

Keywords: Autophagy; Behavioral deficits; Perfluorooctane sulfonate.

MeSH terms

  • Animals
  • Autophagy*
  • Cognition
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins
  • Neurotoxicity Syndromes*

Substances

  • perfluorooctane
  • perfluorooctane sulfonic acid
  • Microtubule-Associated Proteins