Valbenazine promotes body growth via growth hormone signaling during zebrafish embryonic development

瓦贝那嗪在斑马鱼胚胎发育过程中通过生长激素信号促进身体生长

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作者:Zhengkang Su, Ziru Dai, Fengqing Qin, Hai Zhang, Miaomiao Zheng, Ya Zhu, Zhiqian Tong, Weihong Song, Xi Li

Abstract

Vesicular monoamine transporter 2 (VMAT-2) functions by uptake of cytoplasmic monoamines into vesicles for storage. Valbenazine (VBZ) is a newly FDA-approved oral VMAT-2 inhibitor used for the treatment of movement disorders such as tardive dyskinesia (TD), and Tourette syndrome (TS). Clinical data shows that VBZ is a relatively safe drug with no cardiotoxicity or hepatotoxicity. However, the effect of VBZ on embryonic development remains unknown. Here, we use zebrafish larvae as an animal model to demonstrate that VBZ exposure causes premature hatching and increased body size and hyperactivity-like behaviors in zebrafish larvae. In addition, VBZ exposure leads to increased dopamine (DA) and Glutamate (Glu) levels. Moreover, an increase of growth hormone (gh) and enriched PI3K/AKT signaling were found in VBZ-exposed zebrafish larvae, which may explain their accelerated development. In summary, VBZ exposure may be developmentally toxic in zebrafish larvae.

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