Varol, D;
Mildner, A;
Blank, T;
Shemer, A;
Barashi, N;
Yona, S;
David, E;
... Jung, S; + view all
(2017)
Dicer Deficiency Differentially Impacts Microglia of the Developing and Adult Brain.
Immunity
, 46
(6)
1030-1044.e8.
10.1016/j.immuni.2017.05.003.
Preview |
Text
Varol et al 12012017 final.compressed.pdf - Accepted Version Download (4MB) | Preview |
Abstract
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge. After peripheral endotoxin exposure, Dicer-deficient microglia expressed more pro-inflammatory cytokines than wild-type microglia and thereby compromised hippocampal neuronal functions. In contrast, prenatal Dicer ablation resulted in spontaneous microglia activation and revealed a role for Dicer in DNA repair and preservation of genome integrity. Accordingly, Dicer deficiency rendered otherwise radio-resistant microglia sensitive to gamma irradiation. Collectively, the differential impact of the Dicer ablation on microglia of the developing and adult brain highlights the changes these cells undergo with time.
| Type: | Article |
|---|---|
| Title: | Dicer Deficiency Differentially Impacts Microglia of the Developing and Adult Brain |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.immuni.2017.05.003 |
| Publisher version: | http://doi.org/10.1016/j.immuni.2017.05.003 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | DNA damage, LPS, LTP, development, dicer, endotoxin, hippocampus, long-term potentiation, microRNA, microglia, mutagenesis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1561151 |
Archive Staff Only
 |
View Item |
