A metabolic switch towards lipid use in glycolytic muscle is an early pathologic event in a mouse model of Amyotrophic Lateral Sclerosis

section Page 2 line 4: "prior to denervation" is replaced by "at 65 days of age" Results section Page 7: A new subheading entitled "4. NMJ dysfunction could participate to Pdk4 up-regulation" is added to present crush and axotomy experiments in a separate paragraph. Discussion section Page 13: 1st paragraph: the last sentence "However, as it stands, our results do not favor patent denervation as a primary cause of the metabolic switch in ALS." Is removed. We have replaced this sentence by the following sentences: " In the SOD1 mice, denervation events have been detected at 30 days of age through a detailed study of the NMJ by electron microscopy (Vinsant et al, 2013), and impaired neuromuscular transmission has been detected at 28-42 days of age (Rocha et al, 2013), long before the onset of motor symptoms. Here, we showed that, at the same period Pdk4 mRNA levels are comparable to those found in WT mice. Altogether these data show that NMJ dysfunction or destabilization might participate to the Pdk4 mRNA induction. " Discussion section Page 15: 1 paragraph line 3: the end of the sentence "before the onset of denervation and prior to motore neuron death in SOD1G86R mice" is removed. The sentence lines 7-8 telling that "glycolytic defect are due to additional events distinct from denervation." Is now replaced by the two following sentences (lines3-7): " These data, in combination with our sciatic nerve crush and axotomy experiments suggest that glycolytic defects might be due to additional events distinct from denervation. However, early changes of synaptic functionality might contribute to early stages of the metabolic switch, which in turn, could contribute to further NMJ changes and a self-propagating