Nerve injury often causes neuronal loss and glial proliferation, disrupting the delicate balance between neurons and glial cells in the brain. Recently, we have developed an innovative technology to convert internal reactive glial cells into functional neurons inside the mouse brain. Here, we further demonstrate that such glia-to-neuron conversion can rebalance neuron-glia ratio and reverse glial scar back to neural tissue.Specifically, using a severe stab injury model in the mouse cortex, we demonstrated that ectopic expression of NeuroD1 in reactive astrocytes significantly reduced glial reactivity and transformed toxic A1 astrocytes into less harmful astrocytes before neuronal conversion. Importantly, astrocytes were not depleted after neuronal conversion but rather repopulated due to its intrinsic proliferation capability. Remarkably, converting reactive astrocytes into neurons also significantly reduced microgliamediated neuroinflammation. Moreover, accompanying regeneration of new neurons together with repopulation of new astrocytes, blood-brain-barrier was restored and synaptic density was rescued in the injury sites. Together, these results demonstrate that glial scar can be reversed back to neural tissue through rebalancing neuron:glia ratio after glia-to-neuron conversion.
The circadian system can be found in nearly all mammalian organs and cells. The maintenance of circadian rhythms is related to the health of human life. Destroying circadian rhythms has a strong correlation with the emergence of many diseases, such as neurological diseases and cardiovascular diseases. Astrocytes are the most common type of cell in the human central nervous system. In recent years, the autonomous regulatory role of astrocytes in the circadian rhythm of the SCN has received increasing attention. This article aims to briefly introduce the role of SCN astrocytes in maintaining circadian rhythm from three aspects: gene expression of astrocytes, regulation of neurotransmitters by astrocytes, and plasticity of astrocytes. At the same time, this article also reviews the relationship between astrocyte activation and circadian rhythm disorders as a neurological disease, and several drugs targeting astrocytes for the treatment of nervous system diseases related to circadian rhythm disorders were proposed to highlight the potential of targeting SCN astrocytes in the treatment of improving circadian rhythm disorders. Finally, this article summarizes current strategies, future challenges, and therapeutic prospects for astrocyte-targeted therapy to improve circadian rhythm disorders. This review aims to highlight SCN astrocytes’ effect on maintaining the circadian rhythm and their related mechanisms and provide a theoretical basis for the future proposal of targeted treatment strategies with astrocytes.
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