{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:24:27Z","timestamp":1773951867357,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Some organophosphorus compounds can induce delayed neurotoxicity, which is characterized by ataxia, also known as organophosphate-induced delayed neurotoxicity (OPIDN). The underlying mechanism of axonal degeneration and demyelination in OPIDN is still poorly understood, although progress on the studies has been made. Progesterone is an important sex hormone with a neuroprotective effect, and a decrease in progesterone level was observed in the hens with OPIDN. To investigate whether exogenous progesterone offers protective effects in OPIDN and to elucidate the underlying mechanisms, we conducted an investigation with adult hens, which is the typical model animal for OPIDN research. The hens were either administrated with a single dose of the classical OPIDN inducer tri-ortho-cresyl phosphate (TOCP) (750 mg\/kg body weight, p.o.) or were pretreated with progesterone (2 mg\/kg body weight\/day, i.p.) prior to TOCP exposure. The results showed that TOCP exposure induced typical OPIDN signs in hens and caused demyelinating lesions in the sciatic nerves. The pretreatment of progesterone delayed and reduced TOCP-induced gait impairment scores and restored the decreased expression of S-100\u03b2 in the sciatic nerves of TOCP-exposed hens. Moreover, progesterone alleviated the TOCP-induced demyelination of the sciatic nerves. These effects were accompanied by alterations in the protein levels of the ErbB2\/p-Akt signaling pathway. These findings indicate that progesterone effectively attenuates TOCP-induced delayed neurotoxicity and protects against myelin damage. This protective effect may be associated with the suppression of TOCP-induced activation of the ErbB2\/p-Akt pathway, accompanied by the restoration of S-100\u03b2 expression.<\/jats:p>","DOI":"10.3390\/toxics14010007","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:22:27Z","timestamp":1766578947000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alleviation of Tri-o-cresyl Phosphate-Induced Myelin Sheath Damage to Sciatic Nerves by Exogenous Progesterone Pretreatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Pan","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8971-5621","authenticated-orcid":false,"given":"Xiao-Hua","family":"Song","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Yuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1-5 Beichenxilu Road, Beijing 100101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/toxsci\/kfx266","article-title":"Organophosphorus compounds at 80: Some old and new issues","volume":"162","author":"Costa","year":"2018","journal-title":"Toxicol. 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