TY  - JOUR
AU  - Hilton, Brett J
AU  - Husch, Andreas
AU  - Schaffran, Barbara
AU  - Lin, Tien-Chen
AU  - Burnside, Emily R
AU  - Dupraz, Sebastian
AU  - Schelski, Max
AU  - Kim, Jisoo
AU  - Müller, Johannes Alexander
AU  - Schoch, Susanne
AU  - Imig, Cordelia
AU  - Brose, Nils
AU  - Bradke, Frank
TI  - An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury.
JO  - Neuron
VL  - 110
IS  - 1
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2022-00397
SP  - 51 - 69.e7
PY  - 2022
N1  - (CC BY-NC-ND)
AB  - 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.
KW  - Animals
KW  - Axons: metabolism
KW  - Central Nervous System: metabolism
KW  - Mammals
KW  - Mice
KW  - Nerve Regeneration: physiology
KW  - Neurons: metabolism
KW  - Spinal Cord Injuries: metabolism
KW  - Baclofen (Other)
KW  - Munc13 (Other)
KW  - RIM1/2 (Other)
KW  - active zone (Other)
KW  - axon injury (Other)
KW  - axon regeneration (Other)
KW  - spinal cord injury (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34706221
C2  - pmc:PMC8730507
DO  - DOI:10.1016/j.neuron.2021.10.007
UR  - https://pub.dzne.de/record/163651
ER  -