The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation.
Evidence is emerging that the tumour necrosis factor (TNF-alpha) is a potent signal that induces neural stem cell proliferation and migration. We show that NSC self-renewal is controlled by bi-directional cross-talk between the endocannabinoid system and the TNF signalling pathway. By blocking endogenous TNF-alpha activity, we demonstrate that the TNF system is critical for the proliferation of NSC. Furthermore, we show that pharmacological blockade of the CB1/CB2 cannabinoid receptors dramatically suppresses TNF-alpha-induced NSC proliferation. Interestingly, we found that CB1 or CB2 agonists induce NSC proliferation coupled to a significant increase in both TACE/ADAM 17 and TNF-alpha levels. Overall these data suggest a novel mode of action for the endocannabinoid system in NSC proliferation that is coupled to TNF signalling and that may be of therapeutic interest in the emerging field of brain repair.
Rubio-Araiz
Ana
A
Laboratory of Neuroinflammation, Unidad de Neurología Experimental (Research Unit associated to the Instituto Cajal, CSIC, Madrid), Hospital Nacional de Parapléjicos (SESCAM), 45071 Toledo, Spain.
Arévalo-Martín
Angel
A
Gómez-Torres
Oscar
O
Navarro-Galve
Beatriz
B
García-Ovejero
Daniel
D
Suetterlin
Philipp
P
Sánchez-Heras
Elena
E
Molina-Holgado
Eduardo
E
Molina-Holgado
Francisco
F
D000818:Animals; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D063388:Endocannabinoids; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D043882:Receptors, Cannabinoid / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid; D014409:Tumor Necrosis Factor-alpha