Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency

IF 0.9 4区医学 Q4 PATHOLOGY

Journal of Toxicologic Pathology Pub Date : 2024-07-16 DOI:10.1293/tox.2024-0004

Keiko OGATA, Hidenori SUTO, Akira SATO, Keiko MAEDA, Kenta MINAMI, Naruto TOMIYAMA, Tadashi KOSAKA, Hitoshi HOJO, Naofumi TAKAHASHI, Hiroaki AOYAMA, Tomoya YAMADA

{"title":"Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency","authors":"Keiko OGATA, Hidenori SUTO, Akira SATO, Keiko MAEDA, Kenta MINAMI, Naruto TOMIYAMA, Tadashi KOSAKA, Hitoshi HOJO, Naofumi TAKAHASHI, Hiroaki AOYAMA, Tomoya YAMADA","doi":"10.1293/tox.2024-0004","DOIUrl":null,"url":null,"abstract":"In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3–6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design. \n","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"31 1","pages":""},"PeriodicalIF":0.9000,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Toxicologic Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1293/tox.2024-0004","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3–6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design.

查看原文本刊更多论文

大鼠比较甲状腺测定中脑异位形成的最佳测试时间--围产期甲状腺激素不足的下游指标

在过去的一项研究中，我们提出了一种改良的比较甲状腺测定法（CTA），该方法增加了对脑甲状腺激素（TH）浓度和脑组织病理学的检查，但分组规模较小。结果表明，在 Sprague Dawley 大鼠中使用改进的 CTA，可检测到 10 ppm 6-丙基硫脲嘧啶（6-PTU）诱导的后代血清/脑甲状腺激素浓度的显著抑制作用。为了证实定性脑组织病理学的可靠性并确定改良 CTA 中异位（异位神经元群）的最佳检测时间，我们采用类似的研究方案，但动物数量较少（N=3-6/组/次），对 GD20 胎儿和 PND2、4、21 和 28 幼鼠的脑组织病理学以及血清/脑 TH 浓度进行了评估。在 PND21 和 PND28 的幼崽中观察到明显的甲状腺功能减退，脑组织病理学显示有脑异位形成，PND2 和 PND4 的幼崽可能有前驱症状，但在 GD20 胎儿中没有发现。这项研究证实，大鼠 CTA 脑异位的最佳检测时间是 PND21 及以后。这些研究结果表明，在适当的时间进行大脑异位症评估可能是原始 CTA 设计的有效替代方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Toxicologic Pathology PATHOLOGY-TOXICOLOGY

CiteScore

2.10

自引率

16.70%

发文量

审稿时长

>12 weeks

期刊介绍： JTP is a scientific journal that publishes original studies in the field of toxicological pathology and in a wide variety of other related fields. The main scope of the journal is listed below. Administrative Opinions of Policymakers and Regulatory Agencies Adverse Events Carcinogenesis Data of A Predominantly Negative Nature Drug-Induced Hematologic Toxicity Embryological Pathology High Throughput Pathology Historical Data of Experimental Animals Immunohistochemical Analysis Molecular Pathology Nomenclature of Lesions Non-mammal Toxicity Study Result or Lesion Induced by Chemicals of Which Names Hidden on Account of the Authors Technology and Methodology Related to Toxicological Pathology Tumor Pathology; Neoplasia and Hyperplasia Ultrastructural Analysis Use of Animal Models.