An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury_(publisher_version)
Final published version, 10.4 MB, PDF document
Axons in the adult mammalian central nervous system fail to regenerate after spinal cord injury. Neurons lose their capacity to regenerate during development, but the intracellular processes underlying this loss are unclear. We found that critical components of the presynaptic active zone prevent axon regeneration in adult mice. Transcriptomic analysis combined with live-cell imaging revealed that adult primary sensory neurons downregulate molecular constituents of the synapse as they acquire the ability to rapidly grow their axons. Pharmacogenetic reduction of neuronal excitability stimulated axon regeneration after adult spinal cord injury. Genetic gain- and loss-of-function experiments uncovered that essential synaptic vesicle priming proteins of the presynaptic active zone, but not clostridial-toxin-sensitive VAMP-family SNARE proteins, inhibit axon regeneration. Systemic administration of Baclofen reduced voltage-dependent Ca2+ influx in primary sensory neurons and promoted their regeneration after spinal cord injury. These findings indicate that functional presynaptic active zones constitute a major barrier to axon regeneration.
Original language | English |
---|---|
Journal | Neuron |
Volume | 110 |
ISSN | 0896-6273 |
DOIs | |
Publication status | E-pub ahead of print - 19 Oct 2021 |
Externally published | Yes |
Bibliographical note
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
ID: 282873544