Journal Article

DZNE-2022-00397

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png An active vesicle priming machinery suppresses axon regeneration upon adult CNS injury.

Hilton, B. J. (First author)DZNE* ; Husch, A.DZNE* ; Schaffran, B.DZNE* ; Lin, T.-C.DZNE* ; Burnside, E. R.DZNE* ; Dupraz, S.DZNE* ; Schelski, M.DZNE* ; Kim, J.DZNE* ; Müller, J. A. ; Schoch, S. ; Imig, C. ; Brose, N. ; Bradke, F. (Last author)DZNE*

2022
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2021.10.007

Abstract: 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.

Keyword(s): Animals (MeSH) ; Axons: metabolism (MeSH) ; Central Nervous System: metabolism (MeSH) ; Mammals (MeSH) ; Mice (MeSH) ; Nerve Regeneration: physiology (MeSH) ; Neurons: metabolism (MeSH) ; Spinal Cord Injuries: metabolism (MeSH) ; Baclofen ; Munc13 ; RIM1/2 ; active zone ; axon injury ; axon regeneration ; spinal cord injury

Note: (CC BY-NC-ND)

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2022

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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