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

Dyall, S., Mandhair, H. K., Fincham, R. E. A., Kerr, D. M., Roche, M. and 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 (August), pp. 387-395.

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DOI: 10.1016/j.neuropharm.2016.03.055

Abstract

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-1β deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1β 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-1β 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.

Item Type:Article
ISSN:1873-7064
Uncontrolled Keywords:CB1 cannabinoid receptor; CB2 cannabinoid receptor; Docosahexaenoic acid; Endocannabinoids; Eicosapentaenoic acid; Neurogenesis
Subjects:UNSPECIFIED
Group:School of Health and Social Care
ID Code:23380
Deposited By: Unnamed user with email symplectic@symplectic
Deposited On:12 Apr 2016 15:34
Last Modified:24 May 2016 11:16

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