This curve corresponds to the biphasic Dnmt and Folr1 protein levels as well as the spinal regeneration response. We measured global methylation in the spinal cords of animals with combined spinal cord and peripheral nerve injuries, which were subjected to varying doses of i.p. FA given daily starting 3 days prior to the injury and continuing 4 days. n = 12 (uninjured control animals); n (FA dose) = 32 (0 μg/kg); 33 (20 μg/kg); 32 (40 μg/kg); 33 (80 μg/kg); 34 (160 μg/kg); 32 (400 μg/kg); 32 (800 μg/kg). The quadratic term in the dose-response model was statistically significant (P = 0.001), confirming that there is a U-shaped dose response to the folate dose on a log scale. There are no differences between the injured/untreated animals and the animals treated with 20 μg/kg FA (P = 0.99), nor between the animals treated with the 400 μg/kg and 800 μg/kg doses (P = 0.85). Note the tight correlation in the biphasic FA dose effects between global DNA methylation, spinal regeneration (Figure 7F), and the Dnmt3a and Dnmt3b as well as Folr1 protein levels (Figure 7, A–C, and E). The FA dose of 80 μg/kg, at which both DNA methylation and Dnmt3a and Dnmt3b and Folr1 expression levels were maximal, was found to be the most effective in promoting regeneration.