| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Aguareles, José Paraíso-Luna, Juan Palomares, Belén Bajo-Grañeras, Raquel Navarrete, Carmen Ruiz-Calvo, Andrea García-Rincón, Daniel García-Taboada, Elena Guzmán, Manuel Muñoz, Eduardo Galve-Roperh, Ismael |
| 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. |
| Related Links | https://translationalneurodegeneration.biomedcentral.com/counter/pdf/10.1186/s40035-019-0148-x.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20479158 |
| DOI | 10.1186/s40035-019-0148-x |
| Journal | Translational Neurodegeneration |
| Issue Number | 1 |
| Volume Number | 8 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2019-03-08 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Cannabinoid Huntingtin Neurodegeneration Neurogenesis PPAR |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cellular and Molecular Neuroscience Neurology (clinical) Cognitive Neuroscience |
| Journal Impact Factor | 10.8/2023 |
| 5-Year Journal Impact Factor | 11.6/2023 |
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