Background: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder, usually accompanied by neuroblastoma (NB). There is no targeted treatment and animal model of OMS. We aimed to investigate whether insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K) signaling alleviates neuronal cytolysis in pediatric OMS.
Methods: Cultured rat cerebral cortical neurons and cerebellar neurons were incubated with sera or IgG isolated from sera of children with OMS and NB. Cytolysis and PI3K expression were measured by the lactate dehydrogenase assay and enzyme-linked immunosorbent assay, respectively. Using inhibitors and activators, the effects of IGF-1 and PI3K on cytolysis were investigated.
Results: The incubation of sera or IgG from children with OMS and NB increased cytolysis in not only cerebellar neurons, but also cerebral cortical neurons. Furthermore, the IGF-1 receptor antagonist NVP-AEW541 exaggerated cytolysis in children with OMS and NB. IGF-1 alleviated cytolysis, which was blocked by the PI3K inhibitor LY294002. Additionally, sera or IgG from children with OMS and NB compensatively elevated PI3K expression. LY294002 exacerbated cytolysis; whereas, the PI3K activator 740 Y-P suppressed cytolysis.
Conclusion: IGF-1/PI3K signaling alleviates the cytolysis of cultured neurons induced by serum IgG from children with OMS and NB, which may be innovation therapy targets.