Figure 4

NMN accumulates in injured sciatic nerves before degeneration. (A) NMN (a) and NAD (b) levels were determined in mouse sciatic nerves at the indicated time points after nerve transection, and in the contralateral uncut nerve, and normalized to the total adenylate pool (ATP+ADP+AMP) as a measure of nucleotide yield (n=4 per time point; mean±S.E.M., two-way ANOVA with Bonferroni’s post-hoc test, ****P<0.0001). Minor changes in the unlesioned, contralateral nerves likely reflect that they are not completely isolated from the effects of the operation such as anaesthesia and secondary effects. (B) NMN (a) and NAD (b) levels in sciatic nerves lesioned for 30 h of WT and Wld^S mice (n=3–4, one-way ANOVA with Bonferroni’s post-hoc test, **P<0.01). (C) NMN (a) and NAD (b) levels were determined in the whole brain of WT E18.5 embryos (+/+) and of E18.5 embryos of heterozygous (+/gtE) or homozygous (gtE/gtE) for the Nmnat2^gtE allele from which NMNAT2 expression is non-detectable.¹⁸ There is a clear increase in NMN levels in homozygous mice that do not express any NMNAT2 (n=5, one-way ANOVA with Tukey’s post-hoc test, ***P<0.001, ****P<0.0001)