Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury
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 n...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2023-02-01
|
| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216111 |
| _version_ | 1797280987680342016 |
|---|---|
| author | Almir Aljović Anne Jacobi Maite Marcantoni Fritz Kagerer Kristina Loy Arek Kendirli Jonas Bräutigam Luca Fabbio Valérie Van Steenbergen Katarzyna Pleśniar Martin Kerschensteiner Florence M Bareyre |
| author_facet | Almir Aljović Anne Jacobi Maite Marcantoni Fritz Kagerer Kristina Loy Arek Kendirli Jonas Bräutigam Luca Fabbio Valérie Van Steenbergen Katarzyna Pleśniar Martin Kerschensteiner Florence M Bareyre |
| author_sort | Almir Aljović |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:48:07Z |
| format | Article |
| id | doaj.art-55075c5f76d5482b86cf7df9c7d07d56 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:48:07Z |
| publishDate | 2023-02-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-55075c5f76d5482b86cf7df9c7d07d562024-03-03T05:59:49ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-02-01152n/an/a10.15252/emmm.202216111Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injuryAlmir Aljović0Anne Jacobi1Maite Marcantoni2Fritz Kagerer3Kristina Loy4Arek Kendirli5Jonas Bräutigam6Luca Fabbio7Valérie Van Steenbergen8Katarzyna Pleśniar9Martin Kerschensteiner10Florence M Bareyre11Institute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyInstitute of Clinical Neuroimmunology, University Hospital LMU Munich Munich GermanyAbstract 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.https://doi.org/10.15252/emmm.202216111adeno‐associated virusFGF22gene therapyrecoveryspinal cord injury |
| spellingShingle | Almir Aljović Anne Jacobi Maite Marcantoni Fritz Kagerer Kristina Loy Arek Kendirli Jonas Bräutigam Luca Fabbio Valérie Van Steenbergen Katarzyna Pleśniar Martin Kerschensteiner Florence M Bareyre Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury EMBO Molecular Medicine adeno‐associated virus FGF22 gene therapy recovery spinal cord injury |
| title | Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury |
| title_full | Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury |
| title_fullStr | Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury |
| title_full_unstemmed | Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury |
| title_short | Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury |
| title_sort | synaptogenic gene therapy with fgf22 improves circuit plasticity and functional recovery following spinal cord injury |
| topic | adeno‐associated virus FGF22 gene therapy recovery spinal cord injury |
| url | https://doi.org/10.15252/emmm.202216111 |
| work_keys_str_mv | AT almiraljovic synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT annejacobi synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT maitemarcantoni synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT fritzkagerer synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT kristinaloy synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT arekkendirli synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT jonasbrautigam synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT lucafabbio synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT valerievansteenbergen synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT katarzynaplesniar synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT martinkerschensteiner synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury AT florencembareyre synaptogenicgenetherapywithfgf22improvescircuitplasticityandfunctionalrecoveryfollowingspinalcordinjury |