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

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
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DOI:
10.1006/exnr.1999.7306
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发表时间:
2000-02-01
影响因子:
5.3
通讯作者:
Fernyhough, P
Fernyhough, P
中科院分区:
医学2区
文献类型:
--
作者:
Copray, S;Liem, R;Fernyhough, P

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链脲佐菌素糖尿病大鼠比目鱼肌脑源性神经营养因子(BDNF)表达升高。为了确定这种糖尿病引起的升高是否与肌肉活动相关或通过肌肉活动增强,我们通过电刺激坐骨神经诱导高强度肌肉收缩。在6周的糖尿病大鼠中,比目鱼肌的强烈收缩导致BDNF mRNA升高2至4倍,血浆肌酸激酶水平升高,这与严重的局灶性肌纤维损伤和伴随的卫星细胞激活有关。在未受刺激的糖尿病大鼠比目鱼肌中也观察到局灶性肌纤维损伤和伴随的卫星细胞激活,但程度要小得多。在糖尿病指长伸肌(EDL)中,没有观察到肌肉收缩(即实验诱导的或正常日常活动时的肌肉收缩)对肌纤维结构或BDNF mRNA表达的影响。利用电镜非放射性原位杂交技术,糖尿病比目鱼肌中BDNF mRNA的表达升高定位于肌肉纤维和激活的卫星细胞。本研究表明,糖尿病比目鱼肌与糖尿病EDL以及正常动物比目鱼肌和EDL肌相比,极易发生收缩性损伤。糖尿病比目鱼肌的剧烈收缩和相关的肌纤维损伤导致肌纤维中BDNF mRNA的上调和激活的卫星细胞,这可能参与神经/肌肉完整性的恢复和/或维持。(C) 2000年学术出版社。
The expression of brain-derived neurotrophic factor (BDNF) is elevated in the soleus muscle of streptozotocin-diabetic rats. To determine whether this diabetes-induced elevation was associated with or enhanced by muscle activity we have induced high-intensity muscle contraction by electrically stimulating the sciatic nerve. In 6-week diabetic rats, intense contraction of the soleus muscle resulted in a two- to four-fold elevation of BDNF mRNA and increased plasma levels of creatine kinase that were associated with severe focal muscle fiber damage and concomitant satellite cell activation. Focal muscle fiber damage and concomitant satellite cell activation were also observed in the soleus muscle of nonstimulated diabetic rats, but to a much lesser extent. No effects of muscle contraction, i.e., experimentally induced or during normal daily activity, on muscle fiber structure or BDNF mRNA expression were seen in diabetic extensor digitorum longus (EDL) muscle. Using a nonradioactive in situ hybridization technique for electron microscopy, the elevated expression of BDNF mRNA in the diabetic soleus muscle was localized within muscle fibers as web as activated satellite cells. This study shows that diabetic soleus muscle, in contrast to diabetic EDL and to soleus 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 muscle fibers and activated satellite cells, which may be involved in the restoration and/or maintenance of nerve/muscle integrity. (C) 2000 Academic Press.