PUBLICATION
Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity
- Authors
- Hong, T.I., Hwang, K.S., Choi, T.I., Kleinau, G., Scheerer, P., Bang, J.K., Jung, S.H., Kim, C.H.
- ID
- ZDB-PUB-210911-9
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(17): (Journal)
- Registered Authors
- Jung, Seung-Hyun, Kim, Cheol-Hee
- Keywords
- alpha-melanocyte stimulating hormone, autism spectrum disorder, bioassay, melanophore, melanotan-II, zebrafish
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Biological Assay
- Humans
- Larva/drug effects*
- Larva/growth & development
- Melanophores/cytology
- Melanophores/drug effects*
- Peptides, Cyclic/pharmacology*
- Sequence Homology
- Skin Pigmentation*
- Zebrafish
- alpha-MSH/analogs & derivatives*
- alpha-MSH/chemistry
- alpha-MSH/pharmacology*
- PubMed
- 34502223 Full text @ Int. J. Mol. Sci.
Citation
Hong, T.I., Hwang, K.S., Choi, T.I., Kleinau, G., Scheerer, P., Bang, J.K., Jung, S.H., Kim, C.H. (2021) Zebrafish Bioassay for Screening Therapeutic Candidates Based on Melanotrophic Activity. International Journal of Molecular Sciences. 22(17):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping