REVIEW: Developing Peripheral Biochemical Biomarkers of Brain Disorders: Insights from Zebrafish Models

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Nikita P. Ilyin^1,a, Elena V. Petersen^2,b, Tatyana O. Kolesnikova^3,c*, Konstantin A. Demin^1,2,4,5,d*, Sergey L. Khatsko^6,e, Kirill V. Apuhtin^7,8,f, and Allan V. Kalueff^1,4,6,7,g*

¹Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia

²Moscow Institute of Physics and Technology, 115184 Moscow, Russia

³Neuroscience Program, Sirius University of Science and Technology, 354340 Sochi, Russia

⁴Institute of Experimental Medicine, Almazov National Medical Research Centre, Ministry of Healthcare of the Russian Federation, 197341 St. Petersburg, Russia

⁵Laboratory of Preclinical Bioscreening, Granov Russian Research Center of Radiology and Surgical Technologies, Ministry of Healthcare of the Russian Federation, 197758 Pesochny, Russia

⁶Ural Federal University, 620002 Ekaterinburg, Russia

⁷Laboratory of Biopsychiatry, Scientific Research Institute of Neurosciences and Medicine, 630117 Novosibirsk, Russia

⁸Neuroscience Division, Sirius University of Science and Technology, 354340 Sirius Federal Territory, Russia

Received August 22, 2023; Revised January 9, 2024; Accepted February 13, 2024

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High prevalence of human brain disorders necessitates development of the reliable peripheral biomarkers as diagnostic and disease-monitoring tools. In addition to clinical studies, animal models markedly advance studying of non-brain abnormalities associated with brain pathogenesis. The zebrafish (Danio rerio) is becoming increasingly popular as an animal model organism in translational neuroscience. These fish share some practical advantages over mammalian models together with high genetic homology and evolutionarily conserved biochemical and neurobehavioral phenotypes, thus enabling large-scale modeling of human brain diseases. Here, we review mounting evidence on peripheral biomarkers of brain disorders in zebrafish models, focusing on altered biochemistry (lipids, carbohydrates, proteins, and other non-signal molecules, as well as metabolic reactions and activity of enzymes). Collectively, these data strongly support the utility of zebrafish (from a systems biology standpoint) to study peripheral manifestations of brain disorders, as well as highlight potential applications of biochemical biomarkers in zebrafish models to biomarker-based drug discovery and development.

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KEY WORDS: zebrafish, brain disorders, biomarker, peripheral, neurodegeneration, stress, epilepsy

DOI: 10.1134/S0006297924020160

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