Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice
| Autor: | Leibinger, Marco, Zeitler, Charlotte, Gobrecht, Philipp, Andreadaki, Anastasia, Gisselmann, Günter, Fischer, Dietmar |
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| Přispěvatelé: | Ruhr University of Bochum, Projekt DEAL |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
STAT3 Transcription Factor Microinjections Science [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Genetic Vectors Spinal cord injury Severity of Illness Index Article Mice Transduction Genetic Animals Humans ddc:610 Spinal Cord Injuries Janus Kinases Cerebral Cortex Mice Knockout Motor Neurons Interleukin-6 [SDV.BA]Life Sciences [q-bio]/Animal biology PTEN Phosphohydrolase Genetic Therapy Recovery of Function Dependovirus Axons Nerve Regeneration Disease Models Animal Spinal Cord nervous system Raphe Nuclei Female Locomotion Serotonergic Neurons Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Nature Publishing Group, 2021, 12, ⟨10.1038/s41467-020-20112-4⟩ Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-020-20112-4⟩ |
| Popis: | 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. The CNS has limited ability to regenerate following injury, Here, the authors show that a single injection of AAV-hyper-interleukin-6 in the sensory motor cortex results in corticospinal and raphe spinal tracts regeneration in the injured spinal cord as well as functional recovery in mice. |
| Databáze: | OpenAIRE |
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