Methylene Blue Protects against TDP-43 and FUS Neuronal Toxicity in C. elegans and D. rerio
Figure 2
Methylene blue reduces TDP-43 and FUS neuronal toxicity.
mTDP-43 and mFUS transgenics were grown on plates and assayed for various phenotypes. (A) MB reduced mTDP-43 induced paralysis in worms at two doses compared to untreated controls (P<0.001). (B) MB at two doses reduced mFUS induced paralysis in worms compared to untreated controls (P<0.001). (C) Aldicarb induced paralysis for mTDP-43 worms is significantly higher for mTDP-43 worms compared to non-transgenic N2 worms or transgenic wtTDP-43 controls (P<0.001). MB reduced aldicarb induced paralysis of mTDP-43 worms back to non-transgenic N2 and wtTDP-43 levels. (D) Representative photos of motor neuron degeneration phenotypes observed in mTDP-43 transgenic worms. Similar phenotypes were observed for mFUS transgenics. Degeneration is most frequently seen as gaps (white arrows) along neuronal processes. MB reduced the age-dependent degeneration of motor neurons in (E) mTDP-43 and (F) mFUS transgenic worms (*P<0.001 compared to untreated transgenics). MB did not affect the expression of mutant proteins in (G) mTDP-43 or (H) mFUS strains as determined by western blotting of protein extracts from transgenic worms grown with or without MB. Immunoblotting of human lymphoblasts was used as a size control.