Activation of Type 1 Cannabinoid Receptor CB1R Promotes Neurogenesis in Murine Subventricular Zone Cell CulturesReportar como inadecuado

Activation of Type 1 Cannabinoid Receptor CB1R Promotes Neurogenesis in Murine Subventricular Zone Cell Cultures - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor CB1R activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone SVZ stem-progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells Nestin-positive, neurons and astrocytes. Stimulation of the CB1R by R-+-Methanandamide R-m-AEA increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+-+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation without affecting glial differentiation, at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations Ca2+i in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.

Autor: Sara Xapelli, Fabienne Agasse , Laura Sardà-Arroyo, Liliana Bernardino, Tiago Santos, Filipa F. Ribeiro, Jorge Valero, José Bra



Documentos relacionados