Influence of longitudinal radiation exposure from microcomputed tomography scanning on skeletal muscle function and metabolic activity in female CD-1 mice

Abstract

Microcomputed tomography (μCT) is an imaging technology to assess bone microarchitecture, a determinant of bone strength. When measured in vivo, μCT exposes the skeletal site of interest to a dose of radiation, in addition to nearby skeletal muscles as well. Therefore, the aim of this study was to determine the effects of repeated radiation exposure from in vivo μCT on muscle health - specifically, muscle morphometrics, contractile function, and enzyme activity. This study exposed the right hind limb of female mice to either a low (26 cGy) or moderate (46 cGy) dose, at 2, 4, and 6 months of age, while the left hind limb of the same animal was exposed to a single dose at 6 months to serve as a nonirradiated control. Muscle weight, cross-sectional area, isometric contractile function, and representative maximal enzyme activities of amino acid, fatty acid, glucose, and oxidative metabolism in extensor digitorum longus (EDL) and soleus were assessed. Low-dose radiation had no effect. In contrast, moderate-dose radiation resulted in a 5% increase in time-to-peak tension and 16% increase in half-relaxation time of isometric twitches in EDL, although these changes were not seen when normalized to force. Moderate-dose radiation also resulted in an ~33% decrease in citrate synthase activity in soleus but not EDL, with no changes to the other enzymes measured. Thus, three low doses of radiation over 6 months had no effect on contractile function or metabolic enzyme activity in soleus and EDL of female mice. In contrast, three moderate doses of radiation over 6 months induced some effects on metabolic enzyme activity in soleus but not EDL Future studies that wish to investigate muscle tissue that is adjacent to scanned bone should take radiation exposure dose into consideration.

Keywords: Citrate synthase; X‐ray; extensor digitorum longus; soleus.

Figure 1

Representative peak twitch force trace normalized to maximal peak twitch of mice extensor digitorum longus and soleus muscles with and without exposure to the low (26 cGy) radiation by microcomputed tomography scanning. EDL, extensor digitorum longus; SOL, soleus; CON, no radiation exposure; RAD, radiation exposure.

Figure 2

Representative peak twitch force trace normalized to maximal peak twitch of mice extensor digitorum longus and soleus muscles with and without exposure to moderate (46 cGy) radiation by microcomputed tomography scanning. EDL, extensor digitorum longus; SOL, soleus; CON, no radiation exposure; RAD, radiation exposure.

Figure 3

Fold change enzyme activity between radiated and nonradiated mice (A) extensor digitorum longus (EDL) and (B) soleus muscles exposed to low (26 cGy) radiation by microcomputed tomography scanning. Values are mean ± SEM. n = 5–6. CON, no radiation exposure; RAD, radiation exposure; AAT, alanine aminotransferase; BHAD, 3‐hydroxyacyl‐CoA dehydrogenase; CPT, carnitine palmitoyltransferase; HK, hexokinase; CS, citrate synthase; COX, cytochrome c oxidase.

Figure 4

Fold change enzyme activity between radiated and nonradiated mice (A) extensor digitorum longus (EDL) and (B) soleus muscles exposed to moderate (46 cGy) radiation by microcomputed tomography scanning. Values are mean ± SEM. n = 5–6. *Significantly different from CON. CON, no radiation exposure; RAD, radiation exposure; AAT, alanine aminotransferase; BHAD, 3‐hydroxyacyl‐CoA dehydrogenase; CPT, carnitine palmitoyltransferase; HK, hexokinase; CS, citrate synthase; COX, cytochrome c oxidase.