Early decrease of survival signal protein and DNA repair enzyme in spinal motor neuron of presymptomatic transgenic mice with a mutant SOD1 gene

We examined expressions of phosphatidylinositol 3-kinase (PI3-K), Akt and redox factor-1 protein (Ref-1) in the spinal cord of transgenic mice with G93A mutant superoxide dismutase (SOD1) (Tg), a valuable model of human amyotrophic lateral sclerosis (ALS), at early and presymptomatic stage, 18 and 25 weeks of age. Significant decrease of PI3-K, and Akt in Tg/18 mice, and of PI3-K, Akt and Ref-1 in Tg/25 was observed on immunoblotting. Immunohistochemistry revealed the significant decrease of PI3-K, Akt and Ref-1 in spinal motor neurons of Tg/25 mice. No significant loss of anterior horn neurons was detected. Therefore, the decrease of survival signal or impairment of DNA repair in the spinal motor neurons precedes a subsequent death of anterior horn neurons, and may account for the mutant SOD1-mediated motor neuronal death in this model.