| Title: | Lack of preventive effect of maternal exposure to alpha-glycosyl isoquercitrin and alpha-lipoic acid on developmental hypothyroidism-induced aberrations of hippocampal neurogenesis in rat offspring |
| Author(s): | Masubuchi Y; Tanaka T; Okada R; Ito Y; Nakahara J; Kikuchi S; Watanabe Y; Yoshida T; Maronpot RR; Koyanagi M; Hayashi SM; Shibutani M; |
| Address: | "Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. Cooperative Division of Veterinary Sciences, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan. Maronpot Consulting, LLC, 1612 Medfield Road, Raleigh, North Carolina 27607, USA. Global Scientific and Regulatory Affairs, San-Ei Gen F.F.I., Inc., 1-1-11 Sanwa-cho, Toyonaka-shi, Osaka 561-8588, Japan. Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan" |
| ISSN/ISBN: | 0914-9198 (Print) 1881-915X (Electronic) 0914-9198 (Linking) |
| Abstract: | "Hypothyroidism during the developmental stage induces disruption of hippocampal neurogenesis in later life, as well as inducing oxidative stress in the brain. The present study investigated the preventive effect of co-exposure to an antioxidant on disruptive neurogenesis induced by developmental exposure to anti-thyroid agent in rats. For this purpose, we used two antioxidants, alpha-glycosyl isoquercitrin (AGIQ) and alpha-lipoic acid (ALA). Mated female Sprague Dawley rats were either untreated (control) or treated with 12 ppm 6-propyl-2-thiouracil (PTU), an anti-thyroid agent, in drinking water from gestational day 6 to postnatal day (PND) 21, the latter group being subjected to feeding basal diet alone or diet containing AGIQ at 5,000 ppm or ALA at 2,000 ppm during PTU exposure. On PND 21, PTU-exposed offspring showed reductions in a broad range of granule cell lineage subpopulations and a change in the number of GABAergic interneuron subpopulations. Co-exposure of AGIQ or ALA with PTU altered the transcript levels of many genes across multiple functions, suggestive of enhancement of synaptic plasticity and neurogenesis. Nevertheless, immunohistochemical results did not support these changes. PTU exposure and co-exposure of AGIQ or ALA with PTU did not alter the hippocampal lipid peroxidation level. The obtained results suggest a possibility that thyroid hormone depletion itself primarily disrupts neurogenesis and that oxidative stress may not be involved in the disruption during development. Transcript expression changes of many genes caused by antioxidants may be the result of neuroprotective actions of antioxidants rather than their antioxidant activity. However, no preventive effect on neurogenesis suggested impairment of protein synthesis via an effect on mRNA translation due to hypothyroidism" |
| Keywords: | chemoprevention developmental neurotoxicity hippocampal neurogenesis hypothyroidism alpha-glycosyl isoquercitrin alpha-lipoic acid; |
| Notes: | "PubMed-not-MEDLINEMasubuchi, Yasunori Tanaka, Takaharu Okada, Rena Ito, Yuko Nakahara, Junta Kikuchi, Satomi Watanabe, Yousuke Yoshida, Toshinori Maronpot, Robert R Koyanagi, Mihoko Hayashi, Shim-Mo Shibutani, Makoto eng Japan 2019/08/14 J Toxicol Pathol. 2019 Jul; 32(3):165-180. doi: 10.1293/tox.2019-0018. Epub 2019 May 31" |
