Reversing Glial Scar Back To Neural Tissue Through NeuroD1-Mediated Astrocyte-To-Neuron Conversion
| Autor: | Zifei Pei, Swaminnathan, Grace Lee, Yuanting Chen, Fei Wang, Lei Z, Gong Chen, Lei Zhang, Feipeng Zhang, Alice Cai, Guo Z, Mok Yk, Yuting Bai |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Chemistry Regeneration (biology) Nerve injury Cell biology Glial scar 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure nervous system NEUROD1 medicine Ectopic expression Neuron medicine.symptom 030217 neurology & neurosurgery Neuroinflammation 030304 developmental biology Astrocyte |
| DOI: | 10.1101/261438 |
| Popis: | 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 microglia-mediated 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. |
| Databáze: | OpenAIRE |
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