Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associated with elevated expression of brain-derived neurotrophic factor mRNA in muscle fibers and activated satellite cells

The expression of brain-derived neurotrophic factor (BDNF) is elevated in t he soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activ ity we have induced high-intensity muscle contraction by electrically stimu lating the sciatic nerve. In 6-week diabetic rats, intense contraction of t he soleus muscle resulted in a two- to four-fold elevation of BDNF mRNA and increased plasma levels of creatine kinase that were associated with sever e focal muscle fiber damage and concomitant satellite cell activation. Foca l muscle fiber damage and concomitant satellite cell activation were also o bserved in the soleus muscle of nonstimulated diabetic rats, but to a much lesser extent. No effects of muscle contraction, i.e., experimentally induc ed or during normal daily activity, on muscle fiber structure or BDNF mRNA expression were seen in diabetic extensor digitorum longus (EDL) muscle. Us ing a nonradioactive in situ hybridization technique for electron microscop y, the elevated expression of BDNF mRNA in the diabetic soleus muscle was l ocalized within muscle fibers as web as activated satellite cells. This stu dy shows that diabetic soleus muscle, in contrast to diabetic EDL and to so leus and EDL muscle of normal animals, is highly susceptible to contraction -induced damage. Intense contraction and the associated muscle fiber damage in the diabetic soleus muscle result in an upregulation of BDNF mRNA in mu scle fibers and activated satellite cells, which may be involved in the res toration and/or maintenance of nerve/muscle integrity. (C) 2000 Academic Pr ess.