2. Academic Validation
  3. Potential effects of bexarotene on neural development and function in zebrafish embryos

Potential effects of bexarotene on neural development and function in zebrafish embryos

  • Biomed Pharmacother. 2026 Feb:195:119050. doi: 10.1016/j.biopha.2026.119050.
Wenwen Zha 1,  Minglei Wang 2,  Yunlong Meng 3,  Kangyu Liu 3,  Lirong Huang 3,  Haining Li 3,  Nan Yin 3,  Yuanhai Xie 3,  Jiayi Du 3,  Mingxia Song 4,  Zigang Cao 5,  Jianjun Chen 6,  Zilin Zhong 7
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China; Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, College of Traditional Chinese Medicine and Pharmacy, Jinggangshan University, Ji'an 343009, China.
  • 2 Department of Neurosurgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China.
  • 3 Department of Neurosurgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China.
  • 4 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, College of Traditional Chinese Medicine and Pharmacy, Jinggangshan University, Ji'an 343009, China. Electronic address: [email protected].
  • 5 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Development Biology of Organs and Epigenetics, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Clinical Research Center of Affiliated Hospital of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an 343009, China. Electronic address: [email protected].
  • 6 Department of Neurosurgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China. Electronic address: [email protected].
  • 7 Department of Neurosurgery, Putuo People's Hospital, School of Medicine, Tongji University, Shanghai 200060, China; Institute of Medical Genetics, Department of Big Data in Health Science School of Public Health and General Medicine, Tongji University School of Medicine, Tongji University, Shanghai 200331, China. Electronic address: [email protected].
PMID: 41579708 DOI: 10.1016/j.biopha.2026.119050
Abstract

Bexarotene is a retinoid X receptor (RXR) agonist that plays a crucial role in cell growth and differentiation. It has shown potential in treating both early- and late-stage cutaneous T-cell lymphoma (CTCL). However, the impact of Bexarotene on the neurodevelopment of aquatic organisms, particularly aquatic vertebrates, remains poorly understood. This study aimed to investigate the effects of various concentrations of bexarotene (3 μg/L, 6 μg/L, and 9 μg/L) on the development of the zebrafish embryonic nervous system, using zebrafish as a model organism. The underlying molecular mechanisms were explored through a combination of pharmacological interventions, Molecular Biology, histopathology, and transcriptomics. Studies have shown that zebrafish embryos exposed to Bex show significant changes in development, including morphological abnormalities, head malformations, significantly shortened head length and width, reduced fluorescent area, cell Apoptosis, shortened spinal motor neuron axon length, abnormal myelin development, decreased oligodendrocytes, cerebellar developmental damage, and abnormal behavior. Transcriptomics and qPCR results showed abnormal expression of neurodevelopmental genes (OLIG2, mbpa, atoh1a, gfap, ngn1, gap43, etc.). In addition, exposure to medium and high concentrations of bexarotene significantly increased acetylcholinesterase (AChE) activity. Bexarotene activates the Wnt signaling pathway, and treatment with the Wnt Inhibitor IWR-1 can partially rescue the neurodevelopmental impairments in embryos. In summary, bexarotene offers new insights into the potential neurodevelopmental risks in zebrafish embryos, emphasizing the importance of preventing drug side effects and ensuring the safe and rational use of medications to protect the health of living organisms.

Keywords

Axonopathy; Bexarotene; Neurodevelopmental disorders; Zebrafish embryos.

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