Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice
- Spinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This is achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration. We find collaterals of these AAV-transduced motoneurons projecting to serotonergic neurons in both sides of the raphe nuclei. Hence, the transduction of cortical neurons facilitates the axonal transport and release of hIL-6 at innervated neurons in the brain stem. Therefore, this transneuronal delivery of hIL-6 promotes the regeneration of corticospinal and raphespinal fibers after injury, with the latter being essential for hIL-6-induced functional recovery. Thus, transneuronal delivery enables regenerative stimulation of neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.
| Author: | Marco LeibingerGND, Charlotte ZeitlerGND, Philipp GobrechtGND, Anastasia AndreadakiGND, Günter GisselmannGND, Dietmar FischerORCiDGND |
|---|---|
| URN: | urn:nbn:de:hbz:294-99143 |
| DOI: | https://doi.org/10.1038/s41467-020-20112-4 |
| Parent Title (English): | Nature communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | London |
| Document Type: | Article |
| Language: | English |
| Date of Publication (online): | 2023/05/24 |
| Date of first Publication: | 2021/01/15 |
| Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
| Volume: | 12 |
| Issue: | Article 391 |
| First Page: | 391-1 |
| Last Page: | 391-14 |
| Note: | Dieser Beitrag ist auf Grund des DEAL-Springer-Vertrages frei zugänglich. |
| Institutes/Facilities: | Lehrstuhl für Zellphysiologie |
| Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
| open_access (DINI-Set): | open_access |
| faculties: | Medizinische Fakultät |
| Licence (English): |  Creative Commons - CC BY 4.0 - Attribution 4.0 International |
