Fig. 1

Decline in hind-limb grip strength during ALS progression correlates with increase in astrocytes and microglia in the lumbar spinal cord of TDP-43^Q331K mice. a Hind-limb grip strength (N) from NTg, TDP-43^WT and TDP-43^Q331K mice at 3, 10 and 16 months of age. At 3 months, no significant difference in force is present between genotypes. By 10 months, TDP-43^Q331K mice display a significant decrease in hind-limb grip strength compared with both NTg and TDP-43^WT mice (~ 30% reduction; NTg vs TDP-43^Q331K ****P < 0.0001 and TDP-43^WT vs TDP-43^Q331K ++++P < 0.0001; n = 15). A progressive decline in hind-limb grip strength is present at 16 months, with TDP43^Q331K mice showing significantly lower hind-limb grip strength compared with NTg and TDP-43^WT mice (~ 45% reduction; NTg vs TDP-43^Q331K ****P < 0.0001 and TDP-43^WT vs TDP-43^Q331K ++++P < 0.0001; n = 15). b Representative images of the GFAP-positive astrocytes in the lumbar spinal cord of NTg, TDP-43^WT and TDP-43^Q331K animals at 16 months. Dashed line shows the outline of the ventral horn with higher magnification of the white square. Scale bars = 100 μm. c Increased astrocyte expression in TDP-43^Q331K mice (blue bars) compared with NTg (orange bars) and TDP-43^WT mice (green bars) at ages 10 and 16 months (**P < 0.01, ****P < 0.0001; n = 4). d Representative images of CD11b-positive microglia in the lumbar spinal cord of NTg, TDP-43^WT and TDP-43^Q331K animals at 16 months. Dashed line shows the outline of the ventral horn with higher magnification of the white square. Scale bar = 100 μm. e Increased microglia expression in TDP-43^Q331K mice (blue bars) compared with NTg (orange bars) and TDP-43^WT mice (green bars) at ages 10 and 16 months (*P < 0.05, **P < 0.01; n = 4). f Increased number of activated microglia (amoeboid) in TDP-43^Q331K mice (blue bars) compared with NTg (orange bars) and TDP-43^WT (green bars) mice at 10 and 16 months (***P < 0.001, ****P < 0.0001; n = 4). Data are presented as mean ± SEM; one-way ANOVA with Tukey’s post hoc test for each age