论文部分内容阅读
Fragile X syndrome (FXS) is a common inherited mental retardation caused by the lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 gene.Recent studies suggest glia play an important role in the progression of some neurodevelopmental disorders, which including FXS.Here we found that knockout astrocytes from a fragile X mouse cannot support the normal dendritic morphology in the coculture system.Using their conditioned medium, we confirmed Fmrl KO astrocytes caused the abnormal neuronal growth via the neurotoxic factors.Finally, we found that Neurotrophin-3 (NT-3) and glutamate were both elevated released in KO astrocytic conditioned medium (ACM).Moreover, we identified that (1) excessive NT-3 was attributed to the oxidative stress in FXS, (2) increased glutamate synthesis and release was resulted from higher expression of glutaminase and vesicular glutamate transporter2 (VGLUT2) in Fmrl KO astrocytes, (3) overeproduction of NT-3 and glutamate in WT ACM can mimic the abnormal neuronal morphology in KO ACM.Our results support that astrocytes contribute to the dysregulated neurodevelopment of FXS and astrocytic NT-3 or glutamate production could be a therapeutic target for FXS.