Soleus muscle of Down syndrome (DS) mice exhibits elevated markers of oxidative and nitrosative stress

Abstract

Individuals with DS have a reduced capacity for voluntary force generation compared to individuals with and without other forms of intellectual disability. Oxidative stress (OS) is thought to be a key factor in DS pathologies that may be the result of triplication and over‐expression of copper‐zinc superoxide dismutase (CuZnSod). Our aim was to assess markers of OS and nitrosative stress (NS) in soleus muscle of a well established mouse model of DS, the Ts65Dn mouse, which is segmental trisomic for CuZnSod. We hypothesized that soleus muscle of Ts65Dn mice would exhibit elevated markers of OS and NS compared to soleus from wild‐type (WT) controls. Eighteen (n=9 per group) 4–7 month old male Ts65Dn and WT mice were used in these experiments. Western blot analysis was performed to quantify the relative expression of markers of OS (4‐hydroxy‐nonenal (4‐HNE)) and NS (3‐nitrotryosine (3‐NT)). Levels of soleus muscle 4‐HNE and 3‐NT were 476% and 276% higher in Ts65Dn mice (p<0.05), respectively. These findings suggest that soleus muscle from Ts65Dn mice exhibits elevated markers of OS and NS, which is consistent with the human phenotype of DS. Additionally, preliminary microarray analysis identified 43 up‐regulated and 66 down‐regulated genes in soleus of Ts65Dn compared to WT mice (p<0.001, ± 1.5‐fold). We are currently categorizing these differentially expressed genes.Supported by Syracuse University SOE