| First Author | Spiller KJ | Year | 2018 |
| Journal | Nat Neurosci | Volume | 21 |
| Issue | 3 | Pages | 329-340 |
| PubMed ID | 29463850 | Mgi Jnum | J:262408 |
| Mgi Id | MGI:6158749 | Doi | 10.1038/s41593-018-0083-7 |
| Citation | Spiller KJ, et al. (2018) Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy. Nat Neurosci 21(3):329-340 |
| abstractText | Though motor neurons selectively degenerate in amyotrophic lateral sclerosis, other cell types are likely involved in this disease. We recently generated rNLS8 mice in which human TDP-43 (hTDP-43) pathology could be reversibly induced in neurons and expected that microglia would contribute to neurodegeneration. However, only subtle microglial changes were detected during disease in the spinal cord, despite progressive motor neuron loss; microglia still reacted to inflammatory triggers in these mice. Notably, after hTDP-43 expression was suppressed, microglia dramatically proliferated and changed their morphology and gene expression profiles. These abundant, reactive microglia selectively cleared neuronal hTDP-43. Finally, when microgliosis was blocked during the early recovery phase using PLX3397, a CSF1R and c-kit inhibitor, rNLS8 mice failed to regain full motor function, revealing an important neuroprotective role for microglia. Therefore, reactive microglia exert neuroprotective functions in this amyotrophic lateral sclerosis model, and definition of the underlying mechanism could point toward novel therapeutic strategies. |
