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. Author manuscript; available in PMC: 2018 Aug 20.
Published in final edited form as: Nat Neurosci. 2018 Feb 20;21(3):329–340. doi: 10.1038/s41593-018-0083-7

Figure 8. Microglia are necessary for early recovery from MN disease.

Figure 8

(a) Timeline for experiments using PLX3397 to deplete microglia in rNLS8 mice. (b–c) rNLS8 mice given Nutella containing PLX3397 (right), but not control (left) still clasp after 2 weeks on DOX. #, paired t-test, t=3.5, d.f.=4, p=0.02, relative to control mice at 4 weeks off DOX. ***, t=−5.8, d.f.=8, p=0.0004, relative to control mice at 4 weeks off DOX + 2 weeks on. (d) PLX3397-treated mice trend towards reduced evoked CMAP. t=2.3, d.f.=8, p=0.05. (e) PLX3397 treatment reduced the density of IBA-1+ cells in SC. ***, t=5.6, d.f.=8, p=0.0005. (f–h) hTDP-43 (green) is cleared from sham-treated rNLS8 MNs (f), whereas many hTDP-43-positive MNs remain in the PLX3397-treated lumbar SC (g). (h) Quantification of average fluorescence intensity per MN in control (grey) and PLX3397-treated mice (blue) shows that the MNs in microglia-depleted animals are more hTDP-43 immunopositive; **, t=3.3, d.f.= 8, p=0.01. (i) PLX3397-treated mice (n=4) have significantly fewer intact NMJs in their TA muscles than controls. **, t=3.5, d.f.=7, p=0.009. (j–k) Representative cryosections immunostained with CD11b (red) to label microglia and VAChT (green) to label MNs. (l) There are significantly fewer MNs in PLX3397-treated mice compared to control, ***, t=8.7, d.f.=8, p=0.00002. Scale bar= 100 µm. (m–n) Many microglia (IBA-1, red) from control (m) and PLX3397-treated (n) rNLS8 mice express CD68 (blue). Scale bar= 50 µm. Bars represent mean ± S.D., n=5 per group and t-tests unpaired and two-tailed, unless otherwise specified. See Supplementary Table 2 for data summary.