Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity

International Journal of Molecular Sciences

Seung-Hyun Jung¹  Cheol-Hee Kim²  Tae-Ik Choi²  Ted I. Hong²  Jeong Kyu Bang³  Kyu-Seok Hwang⁴  Patrick Scheerer⁵  Gunnar Kleinau⁵ 

[1] Department of Applied Marine Bioresource Science, National Marine Biodiversity Institute of Korea, Seocheon 33662, Korea;Department of Biology, Chungnam National University, Daejeon 34134, Korea;Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Cheongju 28119, Korea;Drug Discovery Platform Research Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea;Group Protein X-ray Crystallography and Signal Transduction, Institute of Medical Physics and Biophysics, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, D-10117 Berlin, Germany;

关键词: zebrafish;    bioassay;    melanophore;    autism spectrum disorder;    alpha-melanocyte stimulating hormone;    melanotan-II;   

DOI  :  10.3390/ijms22179313

来源: DOAJ

【 摘 要 】

In this study, we used the zebrafish animal model to establish a bioassay by which physiological efficacy differential of alpha-melanocyte-stimulating hormone (α-MSH) analogues could be measured by melanosome dispersion in zebrafish larvae. Brain-skin connection research has purported the interconnectedness between the nervous system and skin physiology. Accordingly, the neuropeptide α-MSH is a key regulator in several physiological processes, such as skin pigmentation in fish. In mammals, α-MSH has been found to regulate motivated behavior, appetite, and emotion, including stimulation of satiety and anxiety. Several clinical and animal model studies of autism spectrum disorder (ASD) have already demonstrated the effectiveness of α-MSH in restoring the social deficits of autism. Therefore, we sought to analyze the effect of synthetic and naturally-occurring α-MSH variants amongst different species. Our results showed that unique α-MSH derivatives from several fish species produced differential effects on the degree of melanophore dispersion. Using α-MSH human form as a standard, we could identify derivatives that induced greater physiological effects; particularly, the synthetic analogue melanotan-II (MT-II) exhibited a higher capacity for melanophore dispersion than human α-MSH. This was consistent with previous findings in an ASD mouse model demonstrating the effectiveness of MT-II in improving ASD behavioral symptoms. Thus, the melanophore assay may serve as a useful screening tool for therapeutic candidates for novel drug discovery.

【 授权许可】

Unknown