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

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

doi:10.1016/j.taap.2023.116674

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

Toxicol Appl Pharmacol. 2023 Oct 15:477:116674. doi: 10.1016/j.taap.2023.116674. Epub 2023 Aug 28.

Authors

Zhengkang Su¹, Ziru Dai², Fengqing Qin², Hai Zhang³, Miaomiao Zheng¹, Ya Zhu¹, Zhiqian Tong⁴, Weihong Song⁵, Xi Li⁶

Affiliations

¹ The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, Zhejiang 325000, China.
² Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Beibu Gulf University, Qinzhou 535011, Guangxi, China.
³ College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China.
⁴ Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
⁵ The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, Zhejiang 325000, China; Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: weihong@wmu.edu.cn.
⁶ The Affiliated Kangning Hospital of Wenzhou Medical University, Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, Zhejiang 325000, China. Electronic address: xili_ihb@126.com.

PMID: 37648088
DOI: 10.1016/j.taap.2023.116674

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.

Keywords: Dopamine; VBZ; VMAT2; Zebrafish larvae.