Fig. 5

Sarm1 knockout and haploinsufficiency suppress TDP-43 pathology after rTBI. Representative micrographs showing (A) cortical pTDP-43 expression in Sarm1^+/+, Sarm1^−/−, and Sarm1^+/− mice as well as (B) examples of neurons with different degrees of nuclear expression (long arrows), cytoplasmatic mislocalization (short arrows), and cytoplasmatic accumulation (arrowhead) of pTDP-43 in Sarm1^+/+ mice. Compared to wild type Sarm1^+/+ mice, Sarm1^−/− and Sarm1^+/− mice had significantly (C) attenuated pTDP-43 staining and (D) fewer pTDP-43 positive cells in the injured cerebral cortex at 1 month after rTBI. (E) Both Sarm1^−/− and Sarm1^+/− mice had significantly suppressed cytoplasmatic mislocalization of pTDP-43 in the injured cortex at 1 month. While there was also a reduction in pTDP-43 mislocalization within the non-impacted hemisphere, this effect was only significant in Sarm1^−/− mice. Data are mean ± SEM; n = 9 per group. *p < 0.05, **p < 0.01. Scale bars correspond to 25 μm in (A) and 50 μm in (B)