An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury
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An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury. / Hilton, Brett J; Husch, Andreas; Schaffran, Barbara; Lin, Tien-Chen; Burnside, Emily R; Dupraz, Sebastian; Schelski, Max; Kim, Jisoo; Müller, Johannes Alexander; Schoch, Susanne; Imig, Cordelia; Brose, Nils; Bradke, Frank.
In: Neuron, Vol. 110, 19.10.2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury
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
N1 - Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2021/10/19
Y1 - 2021/10/19
N2 - 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.
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.
U2 - 10.1016/j.neuron.2021.10.007
DO - 10.1016/j.neuron.2021.10.007
M3 - Journal article
C2 - 34706221
VL - 110
JO - Neuron
JF - Neuron
SN - 0896-6273
ER -
ID: 282873544