| Title |
A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways
|
|---|---|
| Published in |
Journal of Neuroimmune Pharmacology, April 2015
|
| DOI | 10.1007/s11481-015-9609-x |
| Pubmed ID | |
| Authors |
Oscar Gomez, Maria A. Sanchez-Rodriguez, Silvia Ortega-Gutierrez, Henar Vazquez-Villa, Carmen Guaza, Francisco Molina-Holgado, Eduardo Molina-Holgado |
| Abstract |
A basal tone of the endocannabinoid 2-arachidonoylglycerol (2-AG) enhances late oligodendrocyte progenitor cell (OPC) differentiation. Here, we investigated whether endogenous 2-AG may also promote OPC proliferation in earlier stages. We found that the blockade of 2-AG synthesizing enzymes, sn-1-diacylglycerol lipases α and β (DAGLs), with RHC-80267 or the antagonism of either CB1 or CB2 cannabinoid receptors with AM281 and AM630, respectively, impaired early OPC proliferation stimulated by platelet-derived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF). On the contrary, increasing the levels of endogenous 2-AG by blocking the degradative enzyme monoacylglycerol lipase (MAGL) with JZL-184, significantly increased OPC proliferation as did agonists of cannabinoid receptor CB1 (ACEA), CB2 (JWH133) or both (HU-210). To elucidate signaling pathways underlying OPC proliferation, we studied the involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and its downstream target mammalian target of rapamycin (mTOR). We show that phosphorylation of Akt and mTOR is required for OPC proliferation stimulated by growth factors (PDGF-AA and bFGF) or by CB1/CB2 agonists (ACEA/JWH133), since it was strongly decreased after LY294002 or rapamycin treatment. In line with this, blockade of CB1 (AM281), CB2 (AM630) or DAGLs (RHC-80267), decreased phosphorylation of Akt, mTOR and 4E-BP1, diminished cyclin E-cdk2 complex association and increased p27(kip1) levels. Our data suggest that proliferation of early OPCs stimulated by PDGF-AA and bFGF depends on the tonic activation of cannabinoid receptors by endogenous 2-AG and provide further evidence on the role of endocannabinoids in oligodendrocyte development, being important for the maintenance and self-renewal of the OPCs. The results highlight the therapeutic potential of the endocannabinoid signaling in the emerging field of brain repair. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 1% |
| Spain | 1 | 1% |
| Hungary | 1 | 1% |
| United States | 1 | 1% |
| Unknown | 64 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 14 | 21% |
| Student > Ph. D. Student | 13 | 19% |
| Student > Bachelor | 11 | 16% |
| Student > Master | 8 | 12% |
| Student > Doctoral Student | 2 | 3% |
| Other | 5 | 7% |
| Unknown | 15 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 12 | 18% |
| Agricultural and Biological Sciences | 12 | 18% |
| Neuroscience | 11 | 16% |
| Medicine and Dentistry | 6 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 4 | 6% |
| Other | 4 | 6% |
| Unknown | 19 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 September 2023.
All research outputs
#7,099,043
of 24,682,395 outputs
Outputs from Journal of Neuroimmune Pharmacology
#201
of 594 outputs
Outputs of similar age
#79,379
of 270,452 outputs
Outputs of similar age from Journal of Neuroimmune Pharmacology
#10
of 20 outputs
Altmetric has tracked 24,682,395 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 594 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has gotten more attention than average, scoring higher than 64% of its peers.
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We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.