Early decrease of survival signal-related proteins in spinal motor neuronsof presymptomatic transgenic mice with a mutant SOD1 gene

The mechanisms of motor neuronal death in amyotrophic lateral sclerosis (AL S) remain to be unclear. Phosphatidy-linositol 3-kinase (PI3-K) and its mai n downstream effector, Akt/protein kinase B (PKB) have been shown to play a central role in neuronal survival against apoptosis supported by neurotrop hic factors. In order to investigate a possible impairment of survival sign aling, we examined expressions of PI3-K and Akt in the spinal cord of the t ransgenic mice overexpressing a mutant Cu/Zn superoxide dismutase (SOD1) ge ne, a valuable model for human ALS. Immunoblotting and immunohistochemical analyses showed that the majority of spinal motor neurons lost the immunore activities for both PI3-K and Akt in the early and presymptomatic stage tha t preceded significant loss of the neurons. The present results suggest tha t an early decrease of survival signal proteins in the spinal motor neurons may account for the subsequent motor neuronal loss in this animal model of ALS.