Arbat-Plana Ariadna, Puigdomenech Maria, Navarro Xavier, Udina Esther
Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Front Cell Neurosci. 2019 Feb 26;13:65. doi: 10.3389/fncel.2019.00065. eCollection 2019.
Physical rehabilitation is one of the cornerstones for the treatment of lesions of the nervous system. After peripheral nerve injuries, activity dependent therapies promote trophic support for the paralyzed muscles, enhance axonal growth and also modulate the maladaptive plastic changes induced by the injury at the spinal level. We have previously demonstrated that an intensive protocol of treadmill running (TR) in rats reduces synaptic stripping on axotomized motoneurons, preserves their perineuronal nets (PNN) and attenuates microglia reactivity. However, it is not clear through which mechanisms exercise is exerting these effects. Here we aimed to evaluate if activation of the locus coeruleus (LC), the noradrenergic center in the brain stem, plays a role in these effects. Since LC is strongly activated during stressful situations, as during intensive exercise, we selectively destroyed the LC by administering the neurotoxin DPS-4 before injuring the sciatic nerve of adult rats. Animals without LC had increased microglia reactivity around injured motoneurons. In these animals, an increasing intensity protocol of TR was not able to prevent synaptic stripping on axotomized motoneurons and the reduction in the thickness of their PNN. In contrast, TR was still able to attenuate microglia reactivity in DSP-4 treated animals, thus indicating that the noradrenergic projections are important for some but not all the effects that exercise induces on the spinal cord after peripheral nerve injury. Moreover, animals subjected to treadmill training showed delayed muscle reinnervation, more evident if treated with DSP-4. However, we did not find differences in treated animals regarding the H/M amplitude ratio, which increased during the first stages of regeneration in all injured groups.
物理康复是治疗神经系统损伤的基石之一。周围神经损伤后，依赖活动的疗法可促进对瘫痪肌肉的营养支持，增强轴突生长，并调节损伤在脊髓水平诱导的适应性不良的可塑性变化。我们之前已经证明，大鼠的高强度跑步机跑步（TR）方案可减少轴突切断的运动神经元上的突触剥离，保留其神经周网（PNN），并减弱小胶质细胞反应性。然而，目前尚不清楚运动是通过何种机制发挥这些作用的。在这里，我们旨在评估蓝斑（LC）的激活，即脑干中的去甲肾上腺素能中心，是否在这些作用中发挥作用。由于LC在应激情况下（如高强度运动期间）会被强烈激活，我们在成年大鼠坐骨神经损伤前通过给予神经毒素DPS-4选择性地破坏了LC。没有LC的动物在损伤的运动神经元周围的小胶质细胞反应性增加。在这些动物中，TR强度增加的方案无法防止轴突切断的运动神经元上的突触剥离及其PNN厚度的减少。相比之下，TR仍然能够减弱DSP-4处理动物中的小胶质细胞反应性，因此表明去甲肾上腺素能投射对于运动在外周神经损伤后对脊髓诱导的某些但不是所有作用都很重要。此外，接受跑步机训练的动物显示出肌肉再支配延迟，如果用DSP-4处理则更明显。然而，我们在处理的动物中未发现H/M振幅比的差异，所有损伤组在再生的第一阶段该比值都会增加。
