科研之友
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摘要
Microglia are resident hematopoietic cells that play important roles in the damaged or degenerating adult nervous system. Microglia are involved in neuropathogenesis of various diseases. Microglia are also essential for neuroprotection and comprise an essential component of the neural stem cell niche. The activation of microglia is an important phenomenon associated with several neurological disorders that arise from infections to developmental abnormalities and behavioral pathologies. Noonan syndrome (NS) is associated with mutations in the PTPN11 gene and also accounts for mental retardation in children. Interestingly, in mouse models of NS, mutations in the PTPN11 gene resulted in dysregulation of neural progenitors. The present study describes the activation of microglia in the NS mouse model, which results in an inflammatory phenotype with expression of IL-1 beta and defective phagocytosis. To test whether microglia from NS mice are important for neural precursor maintenance or self-renewal, embryonic neural precursors from the cortex of WT mice were cultured. Microglia from NS and WT mice were then added to cortical precursor cells which showed that microglia from NS mice inhibited astrogenesis. Together, these results demonstrate that microglia can dysregulate neural precursor development in NS, and suggest that alterations in microglial number as a consequence of genetic or pathological events may perturb neural development by directly affecting embryonic neural precursors.
- 出版日期2011-12
