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Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways.
Br J Pharmacol. 2011 Aug; 163(7):1520-32.BJ

Abstract

BACKGROUND AND PURPOSE

The endogenous cannabinoid system participates in oligodendrocyte progenitor differentiation in vitro. To determine the effect of synthetic cannabinoids on oligodendrocyte differentiation, we exposed differentiating cultures of oligodendrocytes with cannabinoid CB(1), CB(2) and CB(1)/CB(2) receptor agonists and antagonists. The response of the PI3K/Akt and the mammalian target of rapamycin (mTOR) signalling pathways were studied as effectors of cannabinoid activity.

EXPERIMENTAL APPROACH

Purified oligodendrocyte progenitor cells (OPC) obtained from primary mixed glial cell cultures were treated for 48 h with CB(1), CB(2) and CB(1) /CB(2) receptor agonists (ACEA, JWH133 and HU210, respectively) in the presence or absence of the antagonists AM281 (CB(1) receptor) and AM630 (CB(2) receptor). Moreover, inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt and mTOR pathways (LY294002 and rapamycin, respectively) were used to study the involvement of these pathways on cannabinoid-induced OPC maturation.

KEY RESULTS

ACEA, JWH133 and HU-210 enhanced OPC differentiation as assessed by the expression of stage specific antigens and myelin basic protein (MBP). Moreover, this effect was blocked by the CB receptor antagonists. ACEA, JWH133 and HU210 induced a time-dependent phosphorylation of Akt and mTOR, whereas the inhibitors of PI3K/Akt (LY294002) or of mTOR (rapamycin) reversed the effects of HU-210 on oligodendrocyte differentiation and kinase activation.

CONCLUSIONS AND IMPLICATIONS

Activation of cannabinoid CB(1) or CB(2) receptors with selective agonists accelerated oligodendrocyte differentiation through the mTOR and Akt signalling pathways.

Authors+Show Affiliations

Laboratory of Neuroinflammation, Unidad de Neurologia Experimental, Hospital Nacional de Parapléjicos (SESCAM), Toledo, Spain.No 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

21480865

Citation

Gomez, O, et al. "Cannabinoid Receptor Agonists Modulate Oligodendrocyte Differentiation By Activating PI3K/Akt and the Mammalian Target of Rapamycin (mTOR) Pathways." British Journal of Pharmacology, vol. 163, no. 7, 2011, pp. 1520-32.
Gomez O, Sanchez-Rodriguez A, Le M, et al. Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways. Br J Pharmacol. 2011;163(7):1520-32.
Gomez, O., Sanchez-Rodriguez, A., Le, M., Sanchez-Caro, C., Molina-Holgado, F., & Molina-Holgado, E. (2011). Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways. British Journal of Pharmacology, 163(7), 1520-32. https://doi.org/10.1111/j.1476-5381.2011.01414.x
Gomez O, et al. Cannabinoid Receptor Agonists Modulate Oligodendrocyte Differentiation By Activating PI3K/Akt and the Mammalian Target of Rapamycin (mTOR) Pathways. Br J Pharmacol. 2011;163(7):1520-32. PubMed PMID: 21480865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid receptor agonists modulate oligodendrocyte differentiation by activating PI3K/Akt and the mammalian target of rapamycin (mTOR) pathways. AU - Gomez,O, AU - Sanchez-Rodriguez,A, AU - Le,Mqu, AU - Sanchez-Caro,C, AU - Molina-Holgado,F, AU - Molina-Holgado,E, PY - 2011/4/13/entrez PY - 2011/4/13/pubmed PY - 2012/1/19/medline SP - 1520 EP - 32 JF - British journal of pharmacology JO - Br J Pharmacol VL - 163 IS - 7 N2 - BACKGROUND AND PURPOSE: The endogenous cannabinoid system participates in oligodendrocyte progenitor differentiation in vitro. To determine the effect of synthetic cannabinoids on oligodendrocyte differentiation, we exposed differentiating cultures of oligodendrocytes with cannabinoid CB(1), CB(2) and CB(1)/CB(2) receptor agonists and antagonists. The response of the PI3K/Akt and the mammalian target of rapamycin (mTOR) signalling pathways were studied as effectors of cannabinoid activity. EXPERIMENTAL APPROACH: Purified oligodendrocyte progenitor cells (OPC) obtained from primary mixed glial cell cultures were treated for 48 h with CB(1), CB(2) and CB(1) /CB(2) receptor agonists (ACEA, JWH133 and HU210, respectively) in the presence or absence of the antagonists AM281 (CB(1) receptor) and AM630 (CB(2) receptor). Moreover, inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt and mTOR pathways (LY294002 and rapamycin, respectively) were used to study the involvement of these pathways on cannabinoid-induced OPC maturation. KEY RESULTS: ACEA, JWH133 and HU-210 enhanced OPC differentiation as assessed by the expression of stage specific antigens and myelin basic protein (MBP). Moreover, this effect was blocked by the CB receptor antagonists. ACEA, JWH133 and HU210 induced a time-dependent phosphorylation of Akt and mTOR, whereas the inhibitors of PI3K/Akt (LY294002) or of mTOR (rapamycin) reversed the effects of HU-210 on oligodendrocyte differentiation and kinase activation. CONCLUSIONS AND IMPLICATIONS: Activation of cannabinoid CB(1) or CB(2) receptors with selective agonists accelerated oligodendrocyte differentiation through the mTOR and Akt signalling pathways. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21480865/Cannabinoid_receptor_agonists_modulate_oligodendrocyte_differentiation_by_activating_PI3K/Akt_and_the_mammalian_target_of_rapamycin__mTOR__pathways_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01414.x DB - PRIME DP - Unbound Medicine ER -