| Abstract No.: | C-C3098 |
| Country: | Canada |
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| Title: | ACTIVATED MICROGLIA INDUCE APOPTOSIS IN NEURAL PRECURSOR CELLS |
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| Authors/Affiliations: | 1 Rasha Shaikh*; 1 Sean Cregan;
1 Robarts Research Institute, London, ON, Canada
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| Content: | Neuro-inflammation is a common feature of stroke and neurodegenerative disease pathologies. Recent evidence indicates that transplanted neural precursor cells (NPCs) migrate towards sites of inflammation, however, once there, their propensity to undergo cell death has proven to be a major limiting factor. Objective: In this present study, we examine the effect of activated microglia, innate immune cells of the central nervous system, on the proliferation and survival of primary NPCs and define apoptotic signalling pathways that they initiate. Material and methods: NPCs derived from the striatum of E12-13 mouse embryos were cultured in conditioned media (CM) from either unactivated or LPS/IFNγ-activated microglia. Proliferation was examined using neurosphere assays and apoptosis was assessed by nuclear morphology and caspase-3 activity assays. In addition, the expression of pro-apoptotic Bcl-2 family members was analyzed by quantitative RT-PCR. Results: We have determined that neurosphere formation is significantly inhibited in NPCs cultured in activated microglia CM. Moreover, NPCs cultured in activated microglia CM exhibited a significant increase in caspase-3 activity and apoptotic cell death as compared to NPCs cultured in unactivated CM. Additionally, these NPCs demonstrated a significant induction in the expression of the BH3-only Bcl-2 family members: Puma and Noxa. Finally, we have found that Puma-deficient NPCs are less sensitive to activated microglia induced apoptosis. Conclusion: Together these results identify active microglia as a potential trigger of apoptosis in NPCs and suggest that PUMA may be an important therapeutic target for more effective transplantation therapies. |
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