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.
Original language | English |
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Pages (from-to) | 387-395 |
Journal | NEUROPHARMACOLOGY |
Volume | 107 |
Early online date | 1 Apr 2016 |
DOIs | |
Publication status | Published - 1 Apr 2016 |
Keywords
- Animals
- Cell Survival
- Cerebral Cortex
- Docosahexaenoic Acids
- Dose-Response Relationship, Drug
- Eicosapentaenoic Acid
- Endocannabinoids
- Mice
- Mice, Inbred C57BL
- Neural Stem Cells
- Neurogenesis
- Signal Transduction
- Journal Article
Profiles
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Simon Dyall
- School of Life and Health Sciences - Senior Lecturer
- Centre for Integrated Research in Life and Health Sciences
Person: Academic
-
Francisco Molina-Holgado
- School of Life and Health Sciences - Associate Professor
- Centre for Integrated Research in Life and Health Sciences
Person: Academic