Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury
In a recent study, we showed that GABA and baclofen (a GABAB receptor agonist) inhibit caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury (Romaus-Sanjurjo et al., 2018a). Now, we repeated these treatments and perfor...
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00173/full |
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| author | Daniel Sobrido-Cameán Diego Robledo Daniel Romaus-Sanjurjo Vanessa Pérez-Cedrón Laura Sánchez María Celina Rodicio Antón Barreiro-Iglesias |
| author_facet | Daniel Sobrido-Cameán Diego Robledo Daniel Romaus-Sanjurjo Vanessa Pérez-Cedrón Laura Sánchez María Celina Rodicio Antón Barreiro-Iglesias |
| author_sort | Daniel Sobrido-Cameán |
| collection | DOAJ |
| description | In a recent study, we showed that GABA and baclofen (a GABAB receptor agonist) inhibit caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury (Romaus-Sanjurjo et al., 2018a). Now, we repeated these treatments and performed 2 independent Illumina RNA-Sequencing studies in the brainstems of control and GABA or baclofen treated animals. GABA treated larval sea lampreys with their controls were analyzed 29 days after a complete spinal cord injury and baclofen treated larvae with their controls 9 days after the injury. One of the most significantly downregulated genes after both treatments was a HES gene (HESB). HES proteins are transcription factors that are key mediators of the Notch signaling pathway and gamma-secretase activity is crucial for the activation of this pathway. So, based on the RNA-Seq results we subsequently treated spinal cord injured larval sea lampreys with a novel gamma-secretase inhibitor (PF-3804014). This treatment also reduced the expression of HESB in the brainstem and significantly enhanced the regeneration of individually identifiable descending neurons after a complete spinal cord injury. Our results show that gamma-secretase could be a novel target to promote axon regeneration after nervous system injuries. |
| first_indexed | 2024-12-14T10:09:26Z |
| format | Article |
| id | doaj.art-94f95f5cc8ae4e998e8999c2ae62e9f0 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T10:09:26Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-94f95f5cc8ae4e998e8999c2ae62e9f02022-12-21T23:07:03ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-03-01810.3389/fcell.2020.00173520785Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord InjuryDaniel Sobrido-Cameán0Diego Robledo1Daniel Romaus-Sanjurjo2Vanessa Pérez-Cedrón3Laura Sánchez4María Celina Rodicio5Antón Barreiro-Iglesias6Department of Functional Biology, CIBUS, Faculty of Biology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainThe Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Edinburgh, United KingdomDepartment of Functional Biology, CIBUS, Faculty of Biology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Genetics, Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Genetics, Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Functional Biology, CIBUS, Faculty of Biology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainDepartment of Functional Biology, CIBUS, Faculty of Biology, Universidade de Santiago de Compostela, Santiago de Compostela, SpainIn a recent study, we showed that GABA and baclofen (a GABAB receptor agonist) inhibit caspase activation and promote axon regeneration in descending neurons of the sea lamprey brainstem after a complete spinal cord injury (Romaus-Sanjurjo et al., 2018a). Now, we repeated these treatments and performed 2 independent Illumina RNA-Sequencing studies in the brainstems of control and GABA or baclofen treated animals. GABA treated larval sea lampreys with their controls were analyzed 29 days after a complete spinal cord injury and baclofen treated larvae with their controls 9 days after the injury. One of the most significantly downregulated genes after both treatments was a HES gene (HESB). HES proteins are transcription factors that are key mediators of the Notch signaling pathway and gamma-secretase activity is crucial for the activation of this pathway. So, based on the RNA-Seq results we subsequently treated spinal cord injured larval sea lampreys with a novel gamma-secretase inhibitor (PF-3804014). This treatment also reduced the expression of HESB in the brainstem and significantly enhanced the regeneration of individually identifiable descending neurons after a complete spinal cord injury. Our results show that gamma-secretase could be a novel target to promote axon regeneration after nervous system injuries.https://www.frontiersin.org/article/10.3389/fcell.2020.00173/fullnotchgamma-secretaseaxon regenerationGABAbaclofenRNA-Seq |
| spellingShingle | Daniel Sobrido-Cameán Diego Robledo Daniel Romaus-Sanjurjo Vanessa Pérez-Cedrón Laura Sánchez María Celina Rodicio Antón Barreiro-Iglesias Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury Frontiers in Cell and Developmental Biology notch gamma-secretase axon regeneration GABA baclofen RNA-Seq |
| title | Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury |
| title_full | Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury |
| title_fullStr | Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury |
| title_full_unstemmed | Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury |
| title_short | Inhibition of Gamma-Secretase Promotes Axon Regeneration After a Complete Spinal Cord Injury |
| title_sort | inhibition of gamma secretase promotes axon regeneration after a complete spinal cord injury |
| topic | notch gamma-secretase axon regeneration GABA baclofen RNA-Seq |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00173/full |
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