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. 2010 Apr 26;120(5):1603–1616. doi: 10.1172/JCI40000

Figure 5. Dhfr bioactivation is essential for folate-mediated CNS regeneration.

Figure 5

Using the SCRM model of afferent spinal regeneration in rats, i.p. MTX was used to inhibit Dhfr, thus preventing the conversion of FA into the bioactive form tetrahydrofolate, as demonstrated in the Dhfr activity assay (A) (n = 5 [uninjured]; n = 5 [injured]; n = 5 [injured and exposed to MTX]; Student’s t test; mean ± SEM; *P = 0.006), with only a small change in protein levels on Western immunoblot (C, D). N, normal (uninjured); Inj, combined spinal cord and sciatic nerve injury. Note that there is minimal or no increase in Dhfr protein and activity levels after spinal cord/sciatic nerve injury. The dose of MTX (400 μg/kg) that determined maximal inhibition with minimal toxicity was selected from a literature review (46, 51, 52). MTX suppressed the regeneration of spinal axons into a nerve graft to below baseline levels (B) (n = 10 [untreated controls]; n = 7 [FA]; n = 7 [MTX]; n = 6 [MTX and FA]). 1-way ANOVA with Bonferroni’s correction; mean ± SEM; *P < 0.05.