Abstract
BackgroundPropofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. Here, we aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway.MethodsThe effect of propofol on neuronal development was demonstrated by a series of in vitro and in vivo experiments. mRNA injections, whole-mount in situ hybridization and immunohistochemistry, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, 5-ethynyl-2′-deoxyuridine labeling, co-immunoprecipitation, and acyl–biotin exchange labeling were used to identify the potential mechanisms of propofol-mediated zisp expression and determine its effect on the specification of retinal cell types.ResultsPropofol impaired the specification of retinal cell types, thereby inhibiting neuronal and glial cell formation in retinas, mainly through the inhibition of Zisp expression. Furthermore, Zisp promoted the stabilization and secretion of a soluble form of the membrane-associated protein Noggin-1, a specific palmitoylation substrate.ConclusionsPropofol caused a severe phenotype during neuronal development in zebrafish. Our findings established a direct link between an anesthetic agent and protein palmitoylation in the regulation of neuronal development. This could be used to investigate the mechanisms via which the improper use of propofol might result in neuronal defects.
Highlights
Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive
Our findings establish a direct link between propofol and the regulation of neuronal development, suggesting that the improper use of propofol might result in defects in the neuronal system
Propofol impairs retinal growth and function in zebrafish To investigate the effect of propofol on zebrafish development, zebrafish embryos were placed in an anesthetic water bath containing 2.5, 5, or 7.5 μg/ml propofol
Summary
Propofol can have adverse effects on developing neurons, leading to cognitive disorders, but the mechanism of such an effect remains elusive. We aimed to investigate the effect of propofol on neuronal development in zebrafish and to identify the molecular mechanism(s) involved in this pathway. Accumulating evidence from animal studies has shown that anesthetics can have adverse effects on developing neurons, leading to persistent cognitive dysfunction [1,2,3]. It has been found that propofol, even at non-toxic doses, can cause neuronal death in the brains of infant mice and lead to brain damage in fetuses and newborns of non-human primates [7, 8]. Genetic studies have shown that deficiency or dysfunction of PAT activity is associated with several neurological disorders. It has been reported that DHHC5 influences neuronal differentiation in cultured DHHC5-GT (gene-trapped) mouse neural stem cells [23]
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