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Wang, Chen

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Wang, Chen

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Author's Publications: search.filters.isAuthorOfPublication.488d5f91-bd8e-4def-9a9a-9546776af76d

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    A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity
    (Public Library of Science, 2017) Cartoni, Romain; Pekkurnaz, Gulcin; Wang, Chen; Schwarz, Thomas; He, Zhigang
    Improving axonal transport in the injured and diseased central nervous system has been proposed as a promising strategy to improve neuronal repair. However, the contribution of each cargo to the repair mechanism is unknown. DRG neurons globally increase axonal transport during regeneration. Because the transport of specific cargos after axonal insult has not been examined systematically in a model of enhanced regenerative capacity, it is unknown whether the transport of all cargos would be modulated equally in injured central nervous system neurons. Here, using a microfluidic culture system we compared neurons co-deleted for PTEN and SOCS3, an established model of high axonal regeneration capacity, to control neurons. We measured the axonal transport of three cargos (mitochondria, synaptic vesicles and late endosomes) in regenerating axons and found that the transport of mitochondria, but not the other cargos, was increased in PTEN/SOCS3 co-deleted axons relative to controls. The results reported here suggest a pivotal role for this organelle during axonal regeneration.
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    Neural activity promotes long distance, target-specific regeneration of adult retinal axons
    (2017) Lim, Jung-Hwan A.; Stafford, Benjamin K.; Nguyen, Phong L.; Lien, Brian V.; Wang, Chen; Zukor, Katherine; He, Zhigang; Huberman, Andrew D.
    Axons in the mammalian central nervous system (CNS) fail to regenerate after injury. Here we show that if retinal ganglion cell (RGC) activity is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate the long distances necessary to re-innervate the brain. Analysis of genetically-labeled RGCs revealed this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in the adult brain.