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甲状腺機能低下による発達神経毒性のシステムズ薬理学

                     

2015/03/18


甲状腺機能低下による発達神経毒性のシステムズ薬理学

芦川芳史1、西村有平1,2,3,4,5、笹川翔太1、村上宗一郎1、弓削瑞葵1、有吉美稚子1、川瀬玲子1、田中利男1,2,3,4,5

1三重大学大学院医学系研究科薬理ゲノミクス(三重大・院・医・薬理ゲノミクス)
2三重大・院・医・システムズ薬理学
3三重大・メディカルゼブラフィッシュ研究センター
4三重大・生命科学研セ・バイオインフォ
5三重大・新産業創成研究拠点

The effect of thyroid hormones on early neurological development is very important. It has been reported that the thyroid hormones deficiency during developmental period may be related to neuropsychiatric disorders. However, little is known about the mechanisms. To clarify the mechanisms, we exposed zebrafish larvae to methimazole and analyzed the effect of the hypothyroidism on the gene expression and the neurobehavior. The mRNA levels of thyroglobulin, thyroid stimulating hormone beta, and, sodium-iodine symporter were significantly increased, whereas the expression of dopamine receptor 2a and brain-derived neurotrophic factor (bdnf) were significantly decreased in zebrafish exposed to methimazole. Movement responding to dark transition of zebrafish exposed to methimazole was significantly lower than that of zebrafish without exposure to methimazole. The hypoactivity of zebrafish exposed to methimazole was rescued by acute treatment with a selective D2-type receptor agonist. The acute treatment of a selective D1-type receptor agonist also tended to rescue the hypoactivity. Our results suggest that disturbance of dopaminergic systems with the suppression of bdnf may be related to developmental neurotoxicity of hypothyroidism.

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第88回日本薬理学会年会