Publication List Japanese
2023/09/13
ゼブラフィッシュ発生毒性学とデジタルトランスフォーメーション
2023/02/21
患者がん移植モデル(PDX)とターゲットバリデーション
2021/06/29
ハイスループットゼブラフィッシュ発生毒性試験プロトコルの確立
2020/05/29
自動ゼブラフィッシュ創薬のインパクト
2019/11/02
患者がん移植ゼブラフィッシュモデルによるプレシジョンメディシン
》Systems Pharmacology of developmental hypothyroidism by methimazole with the behavior related to dopaminergic systems
2014/09/20
Systems Pharmacology of developmental hypothyroidism by methimazole with the behavior related to dopaminergic systems
Yoshifumi Ashikawa1, Yuhei Nishimura1,2,3,4,5, Soichiro Murakami1, Syota Sasagawa1, Miko Kawabata1, Beibei Zhang1, Michiko Ariyoshi1, Noriko Umemoto1,2,3,4,5, and Toshio Tanaka1,2,3,4,5
1Dept. of Mol. and Cell. Pharmacology, Pharmacogeno and Pharmacoinfo, Mie Univ. Grad. Sch. of Med.
2Mie Univ. Medical Zebrafish Research Center
3Dept. of Systems Pharmacology, Mie Univ. Grad. Sch. of Med.
4Dept. of Omics Medicine, Mie Univ. Industrial Technology Innovation Institute
5Dept. of Bioinfo., Mie Univ. Life Sci. Res. Center
The effect of thyroid hormones on early neurological development is very important. It has been reported that the thyroid hormones deficiency may be related to depression, learning disorder, autism, and, ADHD. However, little is known about the mechanisms causing these disorders by hypothyroidism during developmental period. To clarify the mechanisms, we exposed zebrafish to methimazole from 58 to 132 hpf and analyzed the effect of the hypothyroidism on the gene expression of candidate genes and the behavior in response to the light-dark cycle stimulation at 7 dpf. The mRNA levels of thyroglobulin, thyroid stimulating hormone beta, and, sodium-iodine symporter were significantly increased, whereas the expression of dopamine receptor 2a (drd2a) and brain-derived neurotrophic factor (bdnf) were significantly decreased in zebrafish exposed to methimazole. Total distance moved in dark sections 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. We have developed drd2a KO zebrafish using TALEN to analyze the mechanism of the hypoactivity. Our results suggest that the thyroid hormones deficiency induced by methimazole at the development stage affects the behavior control which may be related to dopaminergic systems with the suppression of bdnf.