We show in the SOD1(G93A) mouse model of ALS that recurrent exposure to restraint stress led to an earlier onset of astrogliosis and microglial activation within the spinal cord, accelerated muscular weakness, and a significant decrease in median survival (105 vs. 122 d) when compared to nonstressed animals.
Human familial amyotrophic lateral sclerosis with an H46R mutant Cu/Zn superoxide dismutase (SOD1) gene is characterized by initial muscle weakness and atrophy in the legs and a very long-term clinical course (approximately 15 years).
Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness.
FALS patients with the H46R mutation showed a benign clinical course and stereotype progression of muscular weakness and atrophy beginning from the legs.