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Type-1 (CB1) cannabinoid receptor promotes neuronal differentiation and maturation of neural stem cells.
PLoS One. 2013; 8(1):e54271.Plos

Abstract

Neural stem cells (NSCs) are self-renewing cells that can differentiate into multiple neural lineages and repopulate regions of the brain after injury. We have investigated the role of endocannabinoids (eCBs), endogenous cues that modulate neuronal functions including neurogenesis, and their receptors CB(1) and CB(2) in mouse NSCs. Real-time PCR and Western blot analyses indicated that CB(1) is present at higher levels than CB(2) in NSCs. The eCB anandamide (AEA) or the CB(1)-specific agonist ACEA enhanced NSC differentiation into neurons, but not astrocytes and oligodendrocytes, whereas the CB(2)-specific agonist JWH133 was ineffective. Conversely, the effect of AEA was inhibited by CB(1), but not CB(2), antagonist, corroborating the specificity of the response. CB(1) activation also enhanced maturation of neurons, as indicated by morphometric analysis of neurites. CB(1) stimulation caused long-term inhibition of the ERK1/2 pathway. Consistently, pharmacological inhibition of the ERK1/2 pathway recapitulated the effects exerted by CB(1) activation on neuronal differentiation and maturation. Lastly, gene array profiling showed that CB(1) activation augmented the expression of genes involved in neuronal differentiation while decreasing that of stemness genes. These results highlight the role of CB(1) in the regulation of NSC fate and suggest that its activation may represent a pro-neuronal differentiation signal.

Authors+Show Affiliations

Department of Biomedicine and Prevention, Section of Anatomy, University of Rome Tor Vergata, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23372698

Citation

Compagnucci, Claudia, et al. "Type-1 (CB1) Cannabinoid Receptor Promotes Neuronal Differentiation and Maturation of Neural Stem Cells." PloS One, vol. 8, no. 1, 2013, pp. e54271.
Compagnucci C, Di Siena S, Bustamante MB, et al. Type-1 (CB1) cannabinoid receptor promotes neuronal differentiation and maturation of neural stem cells. PLoS One. 2013;8(1):e54271.
Compagnucci, C., Di Siena, S., Bustamante, M. B., Di Giacomo, D., Di Tommaso, M., Maccarrone, M., Grimaldi, P., & Sette, C. (2013). Type-1 (CB1) cannabinoid receptor promotes neuronal differentiation and maturation of neural stem cells. PloS One, 8(1), e54271. https://doi.org/10.1371/journal.pone.0054271
Compagnucci C, et al. Type-1 (CB1) Cannabinoid Receptor Promotes Neuronal Differentiation and Maturation of Neural Stem Cells. PLoS One. 2013;8(1):e54271. PubMed PMID: 23372698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Type-1 (CB1) cannabinoid receptor promotes neuronal differentiation and maturation of neural stem cells. AU - Compagnucci,Claudia, AU - Di Siena,Sara, AU - Bustamante,Maria Blaire, AU - Di Giacomo,Daniele, AU - Di Tommaso,Monia, AU - Maccarrone,Mauro, AU - Grimaldi,Paola, AU - Sette,Claudio, Y1 - 2013/01/23/ PY - 2012/09/13/received PY - 2012/12/11/accepted PY - 2013/2/2/entrez PY - 2013/2/2/pubmed PY - 2013/7/23/medline SP - e54271 EP - e54271 JF - PloS one JO - PLoS One VL - 8 IS - 1 N2 - Neural stem cells (NSCs) are self-renewing cells that can differentiate into multiple neural lineages and repopulate regions of the brain after injury. We have investigated the role of endocannabinoids (eCBs), endogenous cues that modulate neuronal functions including neurogenesis, and their receptors CB(1) and CB(2) in mouse NSCs. Real-time PCR and Western blot analyses indicated that CB(1) is present at higher levels than CB(2) in NSCs. The eCB anandamide (AEA) or the CB(1)-specific agonist ACEA enhanced NSC differentiation into neurons, but not astrocytes and oligodendrocytes, whereas the CB(2)-specific agonist JWH133 was ineffective. Conversely, the effect of AEA was inhibited by CB(1), but not CB(2), antagonist, corroborating the specificity of the response. CB(1) activation also enhanced maturation of neurons, as indicated by morphometric analysis of neurites. CB(1) stimulation caused long-term inhibition of the ERK1/2 pathway. Consistently, pharmacological inhibition of the ERK1/2 pathway recapitulated the effects exerted by CB(1) activation on neuronal differentiation and maturation. Lastly, gene array profiling showed that CB(1) activation augmented the expression of genes involved in neuronal differentiation while decreasing that of stemness genes. These results highlight the role of CB(1) in the regulation of NSC fate and suggest that its activation may represent a pro-neuronal differentiation signal. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23372698/Type_1__CB1__cannabinoid_receptor_promotes_neuronal_differentiation_and_maturation_of_neural_stem_cells_ L2 - https://dx.plos.org/10.1371/journal.pone.0054271 DB - PRIME DP - Unbound Medicine ER -