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| Status |
Public on Jun 07, 2018 |
| Title |
Neuronal integrity, not activity, drives synaptic material clearance by microglia after CNS injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Phagocytosis of synaptic debris by microglia is critical for CNS development and homeostasis. Less well understood are microglial functions in injured adult brain, where their presumed role is clearance of neuronal debris. Assay of this process is challenging, because the resulting peripheral myeloid-cell engraftment is difficult to dissociate from microglial clearance. The model used here, optic nerve crush injury in adult mouse, stimulates rapid engulfment of synaptic material by microglia residing in the lateral geniculate nucleus (LGN), sufficiently distant from the injury to preclude peripheral-cell engraftment. Pre-injury pharmacological depletion of microglia causes post-injury accumulation of synaptic debris, suggesting that these, not astrocytes, are the dominant post-injury phagocytes. Genetic and pharmacological manipulations revealed that neuronal activity, which regulates microglial engulfment of synaptic debris in development, does not do so in post-injury synaptic material clearance in adulthood, where such clearance depends instead on axonal integrity. RNAseq reveals C1q involvement in clearance of debris by LGN-resident microglia, supporting our finding of its impaired clearance in C1qa-/- and Itgam-/- mice. Our results demonstrate how neurodegenerative debris is cleared by microglial phagocytosis, and offer a model for assaying microglial phagocytic activity and studying its mechanisms and physiological roles.
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| Overall design |
Microglia were isolated from the LGN of adult (2-3 months old) male c57BL/6 mice in either uninjured, one, or three days post bilateral optic nerve crush injury. Cells were isolated by MACS using CD11b magnetic beads.
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| Contributor(s) |
Norris G, Smirnov I, Filiano A, Shadowen H, Cody K, Ravichandran K, Overall CC, Kipnis J |
| Citation missing |
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| Submission date |
Dec 04, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Christopher Overall |
| Organization name |
University of Virginia
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| Department |
Neuroscience
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| Street address |
409 Lane Road
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| City |
Charlottesville |
| State/province |
Virginia |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA420938 |
| SRA |
SRP126052 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107635_norris_lgn_microglia_raw_counts.tsv.gz |
333.3 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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