PDF(Pubmed)
Abstract：
The elimination of ground reaction force (support withdrawal) vastly affects slow postural muscles in terms of their regulation and structure. One of the effects of support withdrawal in this study was an immediate postural muscle inactivation, followed by the daily gradual development of spontaneous activity of the slow postural soleus muscle in response to rat hindlimb suspension to mimic space flight. The origin of this activity is somewhat akin to muscle spasticity after spinal cord injuries and is the result of KCC2 content decline in the spinal cord\'s motor neurons. However, the physiological consequences of unloading-induced spontaneous activity remain unexplored. We have conducted an experiment with the administration of a highly specific KCC2 activator during 7-day unloading. For this experiment, 32 male Wistar rats were divided into 4 groups: C+placebo, C+CLP-290 (100 mg/kg b w), 7HS+placebo, and 7HS+CLP-hindlimb-suspended group with CLP-290 administration (100 mg/kg b w). The soleus muscles of the animals were dissected and analyzed for several proteostasis- and metabolism-related parameters. CLP-290 administration to the unloaded animals led to the upregulation of AMPK downstream (p-ACC) and mTOR targets (p-p70S6k and p-4E-BP) and an enhanced PGC1alpha decrease vs. the 7HS group, but neither prevented nor enhanced atrophy of the soleus muscle or myofiber CSA.
摘要：
消除地面反作用力（支撑撤回）在调节和结构方面会极大地影响缓慢的姿势肌肉。在这项研究中，支持撤回的影响之一是立即的姿势肌肉失活，其次是每天逐渐发展的自发活动的慢姿势比目鱼肌响应大鼠后肢悬吊以模仿太空飞行。这种活动的起源有点类似于脊髓损伤后的肌肉痉挛，是脊髓运动神经元中KCC2含量下降的结果。然而,卸载诱导的自发活动的生理后果仍未被探索。我们已经进行了在7天卸载期间给予高度特异性KCC2激活剂的实验。对于这个实验,32只雄性Wistar大鼠分为4组：C+安慰剂，C+CLP-290（100mg/kgbw），7HS+安慰剂，7HS+CLP-后肢悬吊组给予CLP-290(100mg/kgbw)。解剖动物的比目鱼肌，并分析了几种与蛋白质和代谢相关的参数。CLP-290对无负载动物的给药导致AMPK下游（p-ACC）和mTOR靶标（p-p70S6k和p-4E-BP）的上调，并增强了PGC1alpha的降低与7HS组,但既不能预防也不能增强比目鱼肌或肌纤维CSA的萎缩。
