Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury

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Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury ; day:05 ; month:01 ; year:2023 ; extent:15
EMBO molecular medicine / European Molecular Biology Organization ; (05.01.2023) (gesamt 15)

Urheber
Aljović, Almir
Jacobi, Anne
Marcantoni, Maite
Kagerer, Fritz
Loy, Kristina
Kendirli, Arek
Bräutigam, Jonas
Fabbio, Luca
Van Steenbergen, Valérie
Pleśniar, Katarzyna
Kerschensteiner, Martin
Bareyre, Florence M.

DOI
10.15252/emmm.202216111
URN
urn:nbn:de:101:1-2023010514280556411141
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:33 MESZ

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Beteiligte

  • Aljović, Almir
  • Jacobi, Anne
  • Marcantoni, Maite
  • Kagerer, Fritz
  • Loy, Kristina
  • Kendirli, Arek
  • Bräutigam, Jonas
  • Fabbio, Luca
  • Van Steenbergen, Valérie
  • Pleśniar, Katarzyna
  • Kerschensteiner, Martin
  • Bareyre, Florence M.

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