Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord
GABAergic signaling and GABA<sub>B</sub> receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor ce...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/23/2014 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850106643369426944 |
|---|---|
| author | Davide Gobbo Phillip Rieder Li-Pao Fang Emeline Buttigieg Moritz Schablowski Elisa Damo Nathalie Bosche Eleonora Dallorto Pascal May Xianshu Bai Frank Kirchhoff Anja Scheller |
| author_facet | Davide Gobbo Phillip Rieder Li-Pao Fang Emeline Buttigieg Moritz Schablowski Elisa Damo Nathalie Bosche Eleonora Dallorto Pascal May Xianshu Bai Frank Kirchhoff Anja Scheller |
| author_sort | Davide Gobbo |
| collection | DOAJ |
| description | GABAergic signaling and GABA<sub>B</sub> receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic downregulation of GABA<sub>B</sub> receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord. Our results show that, while GABA<sub>B</sub> receptors do not significantly alter spinal cord myelination under physiological conditions, they distinctly regulate the OPC differentiation and Ca<sup>2+</sup> signaling. In addition, we investigate the impact of OPC-GABA<sub>B</sub> receptors in two models of toxic demyelination, namely, the cuprizone and the lysolecithin models. The genetic downregulation of OPC-GABA<sub>B</sub> receptors protects against demyelination and oligodendrocyte loss. Additionally, we observe the enhanced resilience to cuprizone-induced pathological alterations in OPC Ca<sup>2+</sup> signaling. Our results provide valuable insights into the potential therapeutic implications of manipulating GABA<sub>B</sub> receptors in spinal cord OPCs and deepen our understanding of the interplay between GABAergic signaling and spinal cord OPCs, providing a basis for future research. |
| format | Article |
| id | doaj-art-7d696dd40dfd490c85a08ff72feb5999 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-7d696dd40dfd490c85a08ff72feb59992025-08-20T02:38:46ZengMDPI AGCells2073-44092024-12-011323201410.3390/cells13232014Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal CordDavide Gobbo0Phillip Rieder1Li-Pao Fang2Emeline Buttigieg3Moritz Schablowski4Elisa Damo5Nathalie Bosche6Eleonora Dallorto7Pascal May8Xianshu Bai9Frank Kirchhoff10Anja Scheller11Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyDepartment of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421 Homburg, GermanyGABAergic signaling and GABA<sub>B</sub> receptors play crucial roles in regulating the physiology of oligodendrocyte-lineage cells, including their proliferation, differentiation, and myelination. Therefore, they are promising targets for studying how spinal oligodendrocyte precursor cells (OPCs) respond to injuries and neurodegenerative diseases like multiple sclerosis. Taking advantage of the temporally controlled and cell-specific genetic downregulation of GABA<sub>B</sub> receptors from OPCs, our investigation addresses their specific influence on OPC behavior in the gray and white matter of the mouse spinal cord. Our results show that, while GABA<sub>B</sub> receptors do not significantly alter spinal cord myelination under physiological conditions, they distinctly regulate the OPC differentiation and Ca<sup>2+</sup> signaling. In addition, we investigate the impact of OPC-GABA<sub>B</sub> receptors in two models of toxic demyelination, namely, the cuprizone and the lysolecithin models. The genetic downregulation of OPC-GABA<sub>B</sub> receptors protects against demyelination and oligodendrocyte loss. Additionally, we observe the enhanced resilience to cuprizone-induced pathological alterations in OPC Ca<sup>2+</sup> signaling. Our results provide valuable insights into the potential therapeutic implications of manipulating GABA<sub>B</sub> receptors in spinal cord OPCs and deepen our understanding of the interplay between GABAergic signaling and spinal cord OPCs, providing a basis for future research.https://www.mdpi.com/2073-4409/13/23/2014spinal cordGABA<sub>B</sub> receptorsoligodendrocyte precursor cellsdemyelinationcuprizone |
| spellingShingle | Davide Gobbo Phillip Rieder Li-Pao Fang Emeline Buttigieg Moritz Schablowski Elisa Damo Nathalie Bosche Eleonora Dallorto Pascal May Xianshu Bai Frank Kirchhoff Anja Scheller Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord Cells spinal cord GABA<sub>B</sub> receptors oligodendrocyte precursor cells demyelination cuprizone |
| title | Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord |
| title_full | Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord |
| title_fullStr | Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord |
| title_full_unstemmed | Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord |
| title_short | Genetic Downregulation of GABA<sub>B</sub> Receptors from Oligodendrocyte Precursor Cells Protects Against Demyelination in the Mouse Spinal Cord |
| title_sort | genetic downregulation of gaba sub b sub receptors from oligodendrocyte precursor cells protects against demyelination in the mouse spinal cord |
| topic | spinal cord GABA<sub>B</sub> receptors oligodendrocyte precursor cells demyelination cuprizone |
| url | https://www.mdpi.com/2073-4409/13/23/2014 |
| work_keys_str_mv | AT davidegobbo geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT philliprieder geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT lipaofang geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT emelinebuttigieg geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT moritzschablowski geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT elisadamo geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT nathaliebosche geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT eleonoradallorto geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT pascalmay geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT xianshubai geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT frankkirchhoff geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord AT anjascheller geneticdownregulationofgabasubbsubreceptorsfromoligodendrocyteprecursorcellsprotectsagainstdemyelinationinthemousespinalcord |