Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury.
FGF22
adeno-associated virus
gene therapy
recovery
spinal cord injury
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
08 02 2023
08 02 2023
Historique:
revised:
14
12
2022
received:
01
04
2022
accepted:
15
12
2022
pubmed:
6
1
2023
medline:
10
2
2023
entrez:
5
1
2023
Statut:
ppublish
Résumé
Functional recovery following incomplete spinal cord injury (SCI) depends on the rewiring of motor circuits during which supraspinal connections form new contacts onto spinal relay neurons. We have recently identified a critical role of the presynaptic organizer FGF22 for the formation of new synapses in the remodeling spinal cord. Here, we now explore whether and how targeted overexpression of FGF22 can be used to mitigate the severe functional consequences of SCI. By targeting FGF22 expression to either long propriospinal neurons, excitatory interneurons, or a broader population of interneurons, we establish that FGF22 can enhance neuronal rewiring both in a circuit-specific and comprehensive way. We can further demonstrate that the latter approach can restore functional recovery when applied either on the day of the lesion or within 24 h. Our study thus establishes viral gene transfer of FGF22 as a new synaptogenic treatment for SCI and defines a critical therapeutic window for its application.
Identifiants
pubmed: 36601738
doi: 10.15252/emmm.202216111
pmc: PMC9906383
doi:
Substances chimiques
FGF22 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16111Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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