Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers.
Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers.
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DOI：
10.1186/1471-2202-10-144
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发表时间：
2009-12-04
期刊：
影响因子：
2.4
通讯作者：
Czarkowska-Bauch J
中科院分区：
文献类型：
--
作者：
Macias M;Nowicka D;Czupryn A;Sulejczak D;Skup M;Skangiel-Kramska J;Czarkowska-Bauch J
有假设认为，运动诱导的脑源性神经营养因子（BDNF）的激活可能是脊髓完全横断后动物行走能力改善的原因。正如我们之前所展示的，跑步机运动导致完整脊髓整个神经元网络中BDNF蛋白和mRNA的上调。问题出现了：(i)跑步机运动训练，辅以尾部刺激，如何影响脊髓大鼠突触可塑性相关分子的表达，以及（ii）反应是否与BDNF蛋白水平和分布有关。我们结合突触前终末、突触素和突触锌的标记物，研究了低胸段脊髓训练对腰椎节段腹侧象限BDNF免疫反应性（IR）水平和分布的影响。用改良的Basso-Beattie-Bresnahan量表评估训练对脊椎动物后肢行走的改善。脊椎训练动物的等级在5到11之间，而脊椎训练动物的等级在2到4之间。功能改善与突触前标记物和BDNF分布的变化有关。横断后6周，突触素IR在IX层大神经元周围减少18%，训练使其表达增加30%以上。腹侧角区的突触锌染色水平未发生变化，而腹侧索区的突触锌染色水平在损伤后下降了26%，并在训练后趋于正常化。总的来说，腹角的BDNF IR水平在损伤后升高了22%，但在训练后没有变化。然而，训练改变了BDNF在过程中的分布，并在较长和较厚的过程中占优势。BDNF在腹外侧和背外侧运动核的两类细胞（胞体范围在100-400 μm2和1000 μm2以上）中选择性上调。我们的研究结果表明，并不是BDNF缺陷决定了脊髓动物的功能改善缺失。它们表明，运动核中不同细胞亚群中BDNF的选择性上调导致运动神经元的神经支配发生变化，运动活动通过区域特异性突触前标记物的增加来调节。
It has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF) may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i) how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii) if a response is related to BDNF protein level and distribution. We investigated the effect of training in rats spinalized at low thoracic segments on the level and distribution of BDNF immunoreactivity (IR) in ventral quadrants of the lumbar segments, in conjunction with markers of presynaptic terminals, synaptophysin and synaptic zinc. Training improved hindlimb stepping in spinal animals evaluated with modified Basso-Beattie-Bresnahan scale. Grades of spinal trained animals ranged between 5 and 11, whereas those of spinal were between 2 and 4. Functional improvement was associated with changes in presynaptic markers and BDNF distribution. Six weeks after transection, synaptophysin IR was reduced by 18% around the large neurons of lamina IX and training elevated its expression by over 30%. The level of synaptic zinc staining in the ventral horn was unaltered, whereas in ventral funiculi it was decreased by 26% postlesion and tended to normalize after the training. Overall BDNF IR levels in the ventral horn, which were higher by 22% postlesion, were unchanged after the training. However, training modified distribution of BDNF in the processes with its predominance in the longer and thicker ones. It also caused selective up-regulation of BDNF in two classes of cells (soma ranging between 100-400 μm2 and over 1000 μm2) of the ventrolateral and laterodorsal motor nuclei. Our results show that it is not BDNF deficit that determines lack of functional improvement in spinal animals. They indicate selectivity of up-regulation of BDNF in distinct subpopulations of cells in the motor nuclei which leads to changes of innervation targeting motoneurons, tuned up by locomotor activity as indicated by a region-specific increase of presynaptic markers.