Ghrelin regulates hyperactivity-like behaviors via growth hormone signaling pathway in zebrafish ( Danio rerio )

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1163263
• Main Authors: Guan, Kaiyu, Shan, Chunyan, Guo, Anqi, Gao, Xiang, Li, Xi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.03.2023
• Subjects: ADHD; Animals; behavioral disorder; Endocrinology; ghrelin; Ghrelin - genetics; growth hormone (GH); Growth Hormone - genetics; Growth Hormone - metabolism; Human Growth Hormone - pharmacology; Humans; Signal Transduction; Zebrafish; ADHD; growth hormone (GH); ghrelin; behavioral disorder; zebrafish
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1163263

Ghrelin is originally identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR) and partially acts by stimulating growth hormone (GH) release. Our previous studies have identified as a novel susceptibility gene for human attention-deficit hyperactivity disorder (ADHD), and -depleted zebrafish ( ) display ADHD-like behaviors. However, the underlying molecular mechanism how ghrelin regulates hyperactivity-like behaviors is not yet known. Here, we performed RNA-sequencing analysis using adult zebrafish brains to investigate the underlying molecular mechanisms. We found that mRNA and genes related to the signaling pathway were significantly reduced at transcriptional expression levels. Quantitative polymerase chain reaction (qPCR) was performed and confirmed the downregulation of signaling pathway-related genes in zebrafish larvae and the brain of adult zebrafish. In addition, zebrafish displayed hyperactive and hyperreactive phenotypes, such as an increase in motor activity in swimming test and a hyperreactive phenotype under light/dark cycle stimulation, mimicking human ADHD symptoms. Intraperitoneal injection of recombinant human growth hormone (rhGH) partially rescued the hyperactivity and hyperreactive-like behaviors in mutant zebrafish. Our results indicated that ghrelin may regulate hyperactivity-like behaviors by mediating signaling pathway in zebrafish. And the protective effect of rhGH on zebrafish hyperactivity behavior provides new therapeutic clues for ADHD patients.