PUBLICATION

25-hydroxycholesterol impairs neuronal and muscular development in zebrafish

Authors
Jamadagni, P., Patten, S.A.
ID
ZDB-PUB-190827-3
Date
2019
Source
Neurotoxicology   75: 14-23 (Journal)
Registered Authors
Patten, Shumoogum
Keywords
25-hydroxycholesterol, behavior, neurodegeneration, neurodevelopment, oxysterol, zebrafish
MeSH Terms
  • Animals
  • Cell Survival/drug effects
  • Dose-Response Relationship, Drug
  • Hydroxycholesterols/toxicity*
  • Motor Activity/drug effects
  • Motor Neurons/drug effects
  • Movement/drug effects
  • Muscle Development/drug effects*
  • Neurogenesis/drug effects*
  • Zebrafish/growth & development
PubMed
31449834 Full text @ Neurotoxicology
Abstract
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 hours 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.
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