BFT treatment increased lifespan, improved behavioral deficits, and prevented motor neuron death in P301S mice. (A) Animal weight. No differences were observed following chronic BFT administration. (B) Survival curve. BFT-treated TG mice showed a significant increase in lifespan. **P < 0.01 compared with TG CTL (Gehan–Breslow–Wilcoxon test). (C) EPM and (D) contextual fear conditioning. Long-term treatment with BFT enhanced memory and reduced behavioral hyperactivity and disinhibition. ****P < 0.0001, ***P < 0.001, **P < 0.01 and *P < 0.05 relative to WT CTL. ###P < 0.001, ##P < 0.01 and #P < 0.05 versus WT BFT. *P < 0.05 compared with TG CTL (two-way ANOVA followed by Tukey multiple comparisons test). L3‒L6 regions of the spinal cord, which contain motor neuron pools for the hind limbs, were stained with cresyl violet (E and F) and the SMI32 antibody (H and I), which recognizes an epitope on non-phosphorylated neurofilament of proteins. Stereological counts show a higher number of motor neurons in BTF treated P301S TG mice compared with TG mice on a control diet. Quantitative analysis was carried out in eight sections per animal. Each treatment group was comprised of six mice. **P < 0.01 and *P < 0.05 relative to TG CTL (unpaired t-test). Scale bar: 200 μm at low magnification and 100 μm at high magnification.