Animals
FVB/N males overexpressing the murine G86R SOD1 mutation [15], and C57BL/6 males knockout for the SCD1 gene (The Jackson Laboratory, Bar Harbor, ME) were maintained in our animal facility at 23°C with a 12 hours light/dark cycle. They had water and regular A04 rodent chow ad libitum. SOD1(G86R) mice were 60-, 75-, 90- and 105 days of age. SCD1 knockout mice were 4–6 months old. The corresponding non-transgenic male littermates served as controls. To induce peripheral nerve injury, mice were anesthetized with 100 mg/kg body mass ketamine chlorhydrate and 5 mg/kg body mass xylazine. The sciatic nerve was exposed at the midthigh level, and crushed with a fine forceps for 30 s or sectioned 3 mm long with microscissors. Skin incision was sutured, and mice were allowed to recover. Hind limbs contralateral to the lesion served as controls [16]. To induce SCD deficiency pharmacologically, 4–6 months old mice were fed with A04 chow ad libitum containing 3-(5-methyl-[1], [3], [4]thiadiazol-2-yl)-6-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-pyridazine, or MF-438 (Prestwick Chemical, Illkirch, France), which is an orally bioavailable inhibitor of SCD enzymatic activity [17]. The drug regimen was prepared to contain 0.00625% (w/w) MF-438 (Safe, Augy, France), which provided a daily dose of 10 mg/kg body mass, as calculated on a basis of 4 g of food intake per day and 25 g of averaged body mass.