Universidad Complutense de Madrid
E-Prints Complutense

Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration

Impacto

Downloads

Downloads per month over past year

Aguareles, José and Paraíso Luna, Juan and Palomares, Belén and Bajo-Grañeras, Raquel and Navarrete, Carmen and Ruiz-Calvo, Andrea and García Rincón, Daniel and García-Taboada, Elena and Guzmán, Manuel and Muñoz, Eduardo and Galve Roperh, Ismael (2019) Oral administration of the cannabigerol derivative VCE-003.2 promotes subventricular zone neurogenesis and protects against mutant huntingtin-induced neurodegeneration. Translational Neurodegeneration, 8 (9). pp. 1-15. ISSN 2047-9158

[img]
Preview
PDF
Creative Commons Attribution.

9MB

Official URL: https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-019-0148-x



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


Item Type:Article
Uncontrolled Keywords:Cannabinoid, Huntingtin, Neurodegeneration, Neurogenesis, PPAR
Subjects:Medical sciences > Medicine > Cardiology
Medical sciences > Biology > Biochemistry
ID Code:57136
Deposited On:27 Sep 2019 12:04
Last Modified:01 Oct 2019 09:23

Origin of downloads

Repository Staff Only: item control page