Methylene blue reduces axon defects in zebrafish expressing mutant TDP-43 or FUS.

(A) Appearance of motor neurons in mTDP-43 and mFUS transgenic zebrafish with and without MB treatment. (B) MB reduced the unbranched axon length phenotype of motor neurons in mTDP-43 and mFUS transgenic zebrafish (*P<0.01 compared to untreated transgenics).

Methylene blue reduces oxidative stress in C. elegans and zebrafish transgenics.

Oxidative stress was measured in transgenic worms and zebrafish with the dihydrofluorescein diacetate (DHF) that fluoresces when exposed to intracellular peroxide. (A) mTDP-43 worms, but not wtTDP-43 transgenics have a higher level of oxidative stress when stained with DHF. mTDP-43 worms treated with MB and then stained with DHF show a remarkable reduction in fluorescence. (B) wtFUS worms show no fluorescence when stained with DHF compared to mFUS worms. mFUS worms treated with MB and then stained with DHF showed reduced fluorescence. (C) Wild type (WT) zebrafish and zebrafish expressing wtTDP-43 show very low levels of fluorescence when stained with DHF compared to mTDP-43 fish. Treatment with MB reduced fluorescence in DHF stained fish. (D) Quantification of fluorescence of DHF stained fish shows that MB treatment significantly reduced fluorescence in mTDP-43 fish (*P<0.001, *#P<0.01). (E) MB significantly reduced fluorescence in DHF stained mFUS zebrafish (*P<0.001).