{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:00:36Z","timestamp":1768712436986,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["21K17266"],"award-info":[{"award-number":["21K17266"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["22J11280"],"award-info":[{"award-number":["22J11280"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"JSPS KAKENHI","doi-asserted-by":"publisher","award":["JP25281024"],"award-info":[{"award-number":["JP25281024"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Perfluorooctane sulfonate (PFOS) has been used in a wide variety of industrial and commercial products. The adverse effects of PFOS on the developing brain are becoming of a great concern. However, the molecular mechanisms of PFOS on brain development have not yet been clarified. We investigated the effect of early-life exposure to PFOS on brain development and the mechanism involved. We investigated the change in thyroid hormone (TH)-induced dendrite arborization of Purkinje cells in the primary culture of newborn rat cerebellum. We further examined the mechanism of PFOS on TH signaling by reporter gene assay, quantitative RT-PCR, and type 2 iodothyronine deiodinase (D2) assay. As low as 10\u22127 M PFOS suppressed thyroxine (T4)-, but not triiodothyronine (T3)-induced dendrite arborization of Purkinje cells. Reporter gene assay showed that PFOS did not affect TR\u03b11- and TR\u03b21-mediated transcription in CV-1 cells. RT-PCR showed that PFOS suppressed D2 mRNA expression in the absence of T4 in primary cerebellar cells. D2 activity was also suppressed by PFOS in C6 glioma-derived cells. These results indicate that early-life exposure of PFOS disrupts TH-mediated cerebellar development possibly through the disruption of D2 activity and\/or mRNA expression, which may cause cerebellar dysfunction.<\/jats:p>","DOI":"10.3390\/ijms241612765","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"12765","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Perfluorooctane Sulfonate on Cerebellar Cells via Inhibition of Type 2 Iodothyronine Deiodinase Activity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7424-1016","authenticated-orcid":false,"given":"Yuki","family":"Fujiwara","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5137-1862","authenticated-orcid":false,"given":"Yuhei","family":"Miyasaka","sequence":"additional","affiliation":[{"name":"Gunma University Heavy Ion Medical Center, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayane","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Science, Hirosaki 036-8564, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiharu","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Horie Hospital, Ota 373-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-6604","authenticated-orcid":false,"given":"Winda","family":"Ariyani","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5076-2041","authenticated-orcid":false,"given":"Izuki","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2247-9740","authenticated-orcid":false,"given":"Noriyuki","family":"Koibuchi","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s00204-012-0822-6","article-title":"Neurotoxic effects of perfluoroalkylated compounds: Mechanisms of action and environmental relevance","volume":"86","author":"Mariussen","year":"2012","journal-title":"Arch. 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