Long‐term caloric restriction increases lipid peroxidation, but decreases protein oxidation, in the skeletal muscle of the Cu/Zn‐SOD mutant G93A mouse, an animal model of ALS

Abstract

We previously reported that long-term caloric restriction (CR) improves motor performance but hastens clinical onset, disease progression and endpoint in the G93A mouse, an animal model of amyotrophic lateral sclerosis (ALS) (Hamadeh et al, 2005). We hypothesized that CR would increase oxidative stress, basal levels of which are heightened in this animal model, partly due to a decrease or no change in most antioxidant enzyme activity. Starting at age 40 d, 27 separately-caged G93A mice were randomly divided into two groups: ad libitum (AL, n = 14; 7 females) and CR (n = 13; 7 females), with a diet equal to 60% of AL. We measured markers of oxidative stress (malondialdehyde-MDA and protein carbonyl-PC) and catalase activity in the skeletal muscle of 99-day-old G93A mice. For the red gastrocnemius, MDA was higher in CR vs. AL mice (83%, P < 0.001), and in females vs. males (32%, P = 0.045). For the white gastrocnemius, CR increased MDA by 26% (P = 0.095), with no sex differences. CR decreased PC levels by 60% (P = 0.002) in the red, and 32% (P = 0.003) in the white, gastrocnemius. Catalase activity remained unchanged. We conclude that CR increases lipid peroxidation in the gastrocnemius, with females having higher values than males in the red muscle, of G93A mice. Unexpectedly, CR decreases protein oxidation in this model of ALS. (Supported by Hamilton Health Sciences Foundation and NSERC Canada)