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dc.contributor.authorDyall, S. C.
dc.contributor.authorDyall, Simon C.
dc.contributor.authorMandhair, Harpreet K.
dc.contributor.authorFincham, R. E. A.
dc.contributor.authorKerr, Daniel M.
dc.contributor.authorRoche, Michelle
dc.contributor.authorMolina-Holgado, Francisco
dc.date.accessioned2020-02-06T14:38:27Z
dc.date.available2020-02-06T14:38:27Z
dc.date.issued2016-04-01
dc.identifier.citationDyall, S. C., Mandhair, H. K., Fincham, R. E. A., Kerr, D. M., Roche, M., & Molina-Holgado, F. (2016). Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways. Neuropharmacology, 107, 387-395. doi: https://doi.org/10.1016/j.neuropharm.2016.03.055en_IE
dc.identifier.issn1873-7064
dc.identifier.urihttp://hdl.handle.net/10379/15764
dc.description.abstractEmerging 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 beta deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1 beta 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 beta 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. (C) 2016 Elsevier Ltd. All rights reserved.en_IE
dc.description.sponsorshipWe gratefully acknowledge support from the Dowager Countess Eleanor Peel Trust (UK) ​grant ref: AJT.1064.2.MJA (11/09) [TH-PRCL.FID2228] and Royal Society International Exchange grant (ref: IE 131551). The authors declare no conflicts of interest.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofNeuropharmacologyen
dc.subjectCB1 cannabinoid receptoren_IE
dc.subjectCB2 cannabinoid receptoren_IE
dc.subjectDocosahexaenoic aciden_IE
dc.subjectEndocannabinoidsen_IE
dc.subjectEicosapentaenoic aciden_IE
dc.subjectNeurogenesisen_IE
dc.subjectPROMOTES NEURONAL DIFFERENTIATIONen_IE
dc.subjectCB2 CANNABINOID RECEPTORSen_IE
dc.subjectCENTRAL-NERVOUS-SYSTEMen_IE
dc.subjectAGE-RELATED DECREASESen_IE
dc.subjectRAT-BRAINen_IE
dc.subjectPROGENITOR PROLIFERATIONen_IE
dc.subjectINFLAMMATORY MEDIATORSen_IE
dc.subjectSTEM/PROGENITOR CELLSen_IE
dc.subjectADULT NEUROGENESISen_IE
dc.subjectPRECURSOR CELLSen_IE
dc.titleDistinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathwaysen_IE
dc.typeArticleen_IE
dc.date.updated2020-02-06T13:14:10Z
dc.identifier.doi10.1016/j.neuropharm.2016.03.055
dc.local.publishedsourcehttps://doi.org/10.1016/j.neuropharm.2016.03.055en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderDowager Countess Eleanor Peel Trust (UK)en_IE
dc.contributor.funderRoyal Societyen_IE
dc.internal.rssid11422080
dc.local.contactMichelle Roche, Physiology, Rm2002 Human Biology Building, National University Of Ireland G, University Road. 5427 Email: michelle.roche@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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