Oxysterols have essential effects on brain homeostasis and their levels are often altered in neurodegenerative and neuroinflammatory diseases. Several studies have demonstrated the cytotoxic effects of 25-HC on different cell lines, however, not much is known about its effects on neurons in vivo. In this study, we examined the effects of 25-HC exposure on the nervous system development in the zebrafish. We showed that survival rate of zebrafish embryos/larvae is significantly decreased at doses of 25-HC above 40 μM. 25-HC was found to affect the motility of zebrafish larvae, primary motor axon and muscle morphology. Furthermore, larvae treated with 25-HC showed a reduced neuronal network and number of HuC-positive cells in the brain. An increased cell death was also observed in both the brain and spinal cord of zebrafish treated with 25-HC. Interestingly, administration of 25-HC at later stages of development (24 and 48 h post fertilization) had no detrimental effects on motor axons. Altogether, our findings show that elevated levels of 25-HC may have important consequences on neuronal development and cell survival.
Keywords: 25-hydroxycholesterol; Behavior; Neurodegeneration; Neurodevelopment; Oxysterol; Zebrafish.
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