Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation

So ask your doctor what cannabinoids have to do with stem cell creation in your brain. Do not take 'I don't know' for an answer,  if it can help your recovery demand to know how you can get cannabinoids.  I would go to Italy or Spain to help my recovery. Why doesn't your doctor know anything?
http://www.sciencedirect.com/science/article/pii/S0163782713000544

• Ismael Galve-Roperh^{a, , 1,} ,
• Valerio Chiurchiù^{b, c, 1},
• Javier Díaz-Alonso^a,
• Monica Bari^d,
• Manuel Guzman^a,
• Mauro Maccarrone^{c, e, ,}

• ^a Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, IUIN, CIBERNED and IRYCIS, 28040 Madrid, Spain
• ^b Department of Biomedical Sciences, University of Teramo, 64100 Teramo, Italy
• ^c European Center for Brain Research (CERC)/Santa Lucia Foundation, 00143 Rome, Italy
• ^d Department of Experimental Medicine & Surgery, Tor Vergata University of Rome, 00133 Rome, Italy
• ^e Center of Integrated Research, Campus Bio-Medico University of Rome, 00128 Rome, Italy

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Abstract

Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS). The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB₁) and type-2 (CB₂) cannabinoid receptors] and metabolic enzymes. Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved. Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm). In the ectoderm-derived nervous system, both CB₁ and CB₂ receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB₁ and CB₂ show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery. The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.

Abbreviations

• 2-AG, 2-arachidonoylglycerol;
• AEA, N-arachidonoylethanolamine;
• BDNF, brain derived neurotrophic factor;
• CBD, cannabidiol;
• CBG, cannabigerol;
• CFU-GEMM, colony-forming unit: granulocyte, erythrocyte, macrophage, megakaryocyte;
• CREB, cAMP response element-binding protein;
• CSF, colony-stimulating factors;
• DAGL, diacylglycerol lipase;
• ECB, endocannabinoid;
• ERK, extracellular-signaling regulated protein kinase;
• ES, embryonic stem;
• ECS, endocannabinoid system;
• FAAH, fatty acid amide hydrolase;
• FGF, fibroblast growth factor;
• GAD, glutamate decarboxylase;
• GSK3β, glycogen synthase kina;
• ICM, inner cell mass;
• HSC, hematopoietic stem cells;
• HPC, hematopoietic progenitor cells;
• L1-CAM, L1-cell adhesion molecule;
• MAGL, monoacylglycerol lipase;
• mGluR, metabotropic glutamate receptors;
• mTORC1, mammalian target of rapamycin complex 1;
• NCAM, neural cell adhesion molecule;
• NGF, nerve growth factor;
• NP, neural progenitor/stem cell;
• OEA, N-oleoylethanolamine;
• PEA, N-palmitoylethanolamine;
• PI3K, phosphoinositol 3-kinase;
• PKA, protein kinase-A;
• PPARγ, peroxisome proliferator activated receptors;
• RANKL, receptor activator of nuclear factor kappa-B ligand;
• SVZ, subventricular zone;
• THC, Δ⁹-tetrahydrocannabinol;
• vGlut, vesicular glutamate transporter;
• VZ, ventricular zone