The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice

Ayane Ninomiya, Abdallah Mshaty, Asahi Haijima, Hiroyuki Yajima, Michifumi Kokubo, Miski Aghnia Khairinisa, Winda Ariyani, Yuki Fujiwara, Sumiyasu Ishii, Nobutake Hosoi, Hirokazu Hirai, Izuki Amano*, Noriyuki Koibuchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies showed a possible association between perfluorooctane sulfonate (PFOS) and developmental disabilities. We previously found the specific effects of PFOS exposure on learning and memory, however, its effect on the other developmental disabilities such as motor and social deficits remains unclear. We examined the effect of early lactational PFOS exposure on motor coordination, social activity, and anxiety in male mice. We orally administered a PFOS solution to dams from postnatal day 1–14. At 10 weeks old, we conducted a behavior test battery to evaluate motor performance, social activity, and anxiety, followed by electrophysiology and Western blot analysis. PFOS-exposed mice displayed impaired motor coordination. Whole-cell patch-clamp recordings from Purkinje cells revealed that the short-term and long-term plasticity at parallel fiber-Purkinje cell synapses are affected by PFOS exposure. Western blot analysis indicated that PFOS exposure increased syntaxin binding protein 1 (Munc18-1) and glutamate metabotropic receptor 1 (mGluR1) protein levels, which may be associated with the change in neurotransmitter release from parallel fibers and the level of long-term depression, respectively. The present study demonstrates that lactational PFOS exposure may have disrupted the pre- and postsynaptic plasticity at parallel fiber-Purkinje cell synapses, causing profound, long-lasting abnormal effects on the cerebellar function.

Original languageEnglish
Article number112751
JournalFood and Chemical Toxicology
Volume159
DOIs
Publication statusPublished - 2022 Jan

Keywords

  • Cerebellum
  • Developmental neurotoxicity
  • Motor coordination
  • Perfluorooctane sulfonate
  • Synaptic plasticity

ASJC Scopus subject areas

  • Food Science
  • Toxicology

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