Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration
Abstract Background The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic eff...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Translational Neurodegeneration |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40035-019-0148-x |
| _version_ | 1819035509067874304 |
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| author | José Aguareles Juan Paraíso-Luna Belén Palomares Raquel Bajo-Grañeras Carmen Navarrete Andrea Ruiz-Calvo Daniel García-Rincón Elena García-Taboada Manuel Guzmán Eduardo Muñoz Ismael Galve-Roperh |
| author_facet | José Aguareles Juan Paraíso-Luna Belén Palomares Raquel Bajo-Grañeras Carmen Navarrete Andrea Ruiz-Calvo Daniel García-Rincón Elena García-Taboada Manuel Guzmán Eduardo Muñoz Ismael Galve-Roperh |
| author_sort | José Aguareles |
| collection | DOAJ |
| description | Abstract Background The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids. Methods We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro. Results Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted subventricular zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis. Conclusions The cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration. |
| first_indexed | 2024-12-21T07:50:45Z |
| format | Article |
| id | doaj.art-06f670319187485080ac1fedb5b6f158 |
| institution | Directory Open Access Journal |
| issn | 2047-9158 |
| language | English |
| last_indexed | 2024-12-21T07:50:45Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj.art-06f670319187485080ac1fedb5b6f1582022-12-21T19:11:04ZengBMCTranslational Neurodegeneration2047-91582019-03-018111510.1186/s40035-019-0148-xOral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegenerationJosé Aguareles0Juan Paraíso-Luna1Belén Palomares2Raquel Bajo-Grañeras3Carmen Navarrete4Andrea Ruiz-Calvo5Daniel García-Rincón6Elena García-Taboada7Manuel Guzmán8Eduardo Muñoz9Ismael Galve-Roperh10Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Emerald Health PharmaceuticalsInstituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Abstract Background The administration of certain cannabinoids provides neuroprotection in models of neurodegenerative diseases by acting through various cellular and molecular mechanisms. Many cannabinoid actions in the nervous system are mediated by CB1 receptors, which can elicit psychotropic effects, but other targets devoid of psychotropic activity, including CB2 and nuclear PPARγ receptors, can also be the target of specific cannabinoids. Methods We investigated the pro-neurogenic potential of the synthetic cannabigerol derivative, VCE-003.2, in striatal neurodegeneration by using adeno-associated viral expression of mutant huntingtin in vivo and mouse embryonic stem cell differentiation in vitro. Results Oral administration of VCE-003.2 protected striatal medium spiny neurons from mutant huntingtin-induced damage, attenuated neuroinflammation and improved motor performance. VCE-003.2 bioavailability was characterized and the potential undesired side effects were evaluated by analyzing hepatotoxicity after chronic treatment. VCE-003.2 promoted subventricular zone progenitor mobilization, increased doublecortin-positive migrating neuroblasts towards the injured area, and enhanced effective neurogenesis. Moreover, we demonstrated the proneurogenic activity of VCE-003.2 in embryonic stem cells. VCE-003.2 was able to increase neuroblast formation and striatal-like CTIP2-mediated neurogenesis. Conclusions The cannabigerol derivative VCE-003.2 improves subventricular zone-derived neurogenesis in response to mutant huntingtin-induced neurodegeneration, and is neuroprotective by oral administration.http://link.springer.com/article/10.1186/s40035-019-0148-xCannabinoidHuntingtinNeurodegenerationNeurogenesisPPAR |
| spellingShingle | José Aguareles Juan Paraíso-Luna Belén Palomares Raquel Bajo-Grañeras Carmen Navarrete Andrea Ruiz-Calvo Daniel García-Rincón Elena García-Taboada Manuel Guzmán Eduardo Muñoz Ismael Galve-Roperh Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration Translational Neurodegeneration Cannabinoid Huntingtin Neurodegeneration Neurogenesis PPAR |
| title | Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration |
| title_full | Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration |
| title_fullStr | Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration |
| title_full_unstemmed | Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration |
| title_short | Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration |
| title_sort | oral administration of the cannabigerol derivative vce 003 2 promotes subventricular zone neurogenesis and protects against mutant huntingtin induced neurodegeneration |
| topic | Cannabinoid Huntingtin Neurodegeneration Neurogenesis PPAR |
| url | http://link.springer.com/article/10.1186/s40035-019-0148-x |
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