Abstract
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.
Highlights
Neurons from the CNS normally fail to regenerate their axons after an injury
We further showed by inducing an axonal injury to the STOPf/f; TdTomato; SynCre neurons that the expression of the Cre recombinase persisted during axonal regeneration 20 hours post injury (Fig 1D)
By testing the axonal transport rate of three cargos in a well-established model of CNS neurons with high regenerative capacity, we showed that axonal transport is not globally increased, but rather that mitochondrial transport is modulated and is likely to contribute to the robust axonal regeneration of the Phosphatase and tensin homolog (PTEN)-/-;SOC3-/- neurons
Summary
Neurons from the CNS normally fail to regenerate their axons after an injury. Recently, it has been demonstrated that specific genetic manipulations could achieve robust CNS axons regeneration in vivo. The deletion of the Phosphatase and tensin homolog (PTEN) and the Suppressor of cytokine signaling 3 (SOCS3) or the over-expression of c-Myc have revealed a previously unknown plasticity of the CNS after axonal injury [1,2,3]. These mutants with high regenerative capacity constitute an opportunity to study the key biological events occurring during axonal regeneration. Using the conditioning lesion paradigm, Mar and colleagues showed that the central branches of DRG axons globally increased their vesicular transport during regeneration [4]
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