25-hydroxycholesterol impairs neuronal and muscular development in zebrafish

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.