The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation

Rubio-Araiz, Ana; Arévalo-Martı́n, Ángel; Gómez-Torres, Oscar; Navarro-Galve, Beatriz; Garcı́a-Ovejero, Daniel; Suetterlin, Philipp; Sánchez-Heras, Elena; Molina‐Holgado, Eduardo; Molina-Holgado, Francisco

doi:10.1016/j.mcn.2008.03.010

Cited by 47 publications

(39 citation statements)

References 39 publications

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“…Cultures of NSCs 5 were prepared from the cortex of day 16 (ED16) mice C57BL6 mice Wild Type (WT, Charles River, UK), or interleukin-1β (IL-1) deficient (KO) C57BL/6 mice (obtained from Prof. Yoichiro Iwakura, University of Tokyo, Tokyo, Japan), as described previously (Reynolds and Weiss, 1992;Rubio-Araiz et al, 2008). Briefly, the NSCs were manually dissociated and the cell suspension centrifuged at 500xg for 5 min.…”

Section: Neural Stem Cell (Nsc) Culturesmentioning

confidence: 99%

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

et al. 2016

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Running title: EPA, but not DHA induces proliferation in NSCs Abbreviations: AA, Arachidonic acid, AEA, anandamide, DHA. Docosahexaenoic acid; EPA, eicosapentaenoic acid, 2-AG, 2-arachidonylglycerol 2 Title: Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects.EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1 deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1 deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair.

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Section: Neural Stem Cell (Nsc) Culturesmentioning

confidence: 99%

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

et al. 2016

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“…Of the many ADAMs identified, ADAM10 and 17 are the most highly conserved, with orthologs demonstrated in yeast, drosophila and primitive chordates [5]. These two ADAMs also have established roles in CNS development, promoting stem cell proliferation and migration [6], and mediating adhesion and neurite outgrowth. These functions, which render ADAM10 and 17 strong candidate regulators of tumor stem cell activity, reflect a range of enzymatic and structural interactions.…”

Section: Introductionmentioning

confidence: 99%

A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells

et al. 2012

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“…Notably, treatment with LPS resulted in production of TNF-α [82], which itself seems to have different effects of NSCs/NPCs depending on the species, developmental stage and concentration. We and others showed that TNF-α and subsequent NF-κB activation lead to increased proliferation of SVZ NSCs [85][86][87][88] without affecting their neuronal and glial differentiation. Contrarily to NF-κB, in the central nervous system IRF3 is believed to play a mainly antiinflammatory role (reviewed in [89]).…”

Section: Neural Stem Cells / Neuronal Progenitor Cellsmentioning

confidence: 88%

Controversial Role of Toll-like Receptor 4 in Adult Stem Cells

Zeuner

Bieback

Widera

2015

Stem Cell Rev and Rep

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Adult or somatic stem cells are tissue-resident cells with the ability to proliferate, exhibit self-maintenance as well as to generate new cells with the principal phenotypes of the tissue in response to injury or disease. Due to their easy accessibility and their potential use in regenerative medicine, adult stem cells raise the hope for future personalisable therapies. After infection or during injury, they are exposed to broad range of pathogen or damage-associated molecules leading to changes in their proliferation, migration and differentiation. The sensing of such damage and infection signals is mostly achieved by Toll-Like Receptors (TLRs) with Toll-like receptor 4 being responsible for recognition of bacterial lipopolysaccharides (LPS) and endogenous danger-associated molecular patterns (DAMPs). In this review, we examine the current state of knowledge on the TLR4-mediated signalling in different adult stem cell populations. Specifically, we elaborate on the role of TLR4 and its ligands on proliferation, differentiation and migration of mesenchymal stem cells, hematopoietic stem cells as well as neural stem cells. Finally, we discuss conceptual and technical pitfalls in investigation of TLR4 signalling in stem cells.

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The endocannabinoid system modulates a transient TNF pathway that induces neural stem cell proliferation

Cited by 47 publications

References 39 publications

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways

A-Disintegrin and Metalloprotease (ADAM) 10 and 17 promote self-renewal of brain tumor sphere forming cells

Controversial Role of Toll-like Receptor 4 in Adult Stem Cells

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