Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation.
Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation.
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DOI：
10.1016/j.neuroscience.2011.10.028
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发表时间：
2012-01-03
期刊：
影响因子：
3.3
通讯作者：
Grau, J. W.
中科院分区：
文献类型：
--
作者：
Huie, J. R.;Garraway, S. M.;Baumbauer, K. M.;Hoy, K. C., Jr.;Beas, B. S.;Montgomery, K. S.;Bizon, J. L.;Grau, J. W.
脑源性神经营养因子（BDNF）是脑和脊髓神经可塑性的有效调节因子。本实验使用体内模型系统来证明具有可控刺激的训练增加脊髓BDNF表达并参与促进适应性可塑性的BDNF依赖性过程。脊髓横断大鼠给予腿部电击时，一个后肢是延长（可控刺激）表现出屈曲持续时间的逐步增加。这种简单形式的反应-结果（工具性）学习在电击与腿部位置无关时（不可控制的刺激）是观察不到的。不受控制的电刺激也会引起持续影响，损害学习长达48小时。可控电击训练可以对抗不可控刺激的不良后果，预防和逆转学习缺陷。在这里，它表明，工具训练的保护和恢复效果取决于BDNF。细胞分析表明，可控刺激增加BDNF mRNA的表达和蛋白在腰髓。这些变化与背角内BDNF受体TrkB蛋白的增加有关。证据表明，这些变化在体内发挥功能作用。BDNF抑制剂（TrkB-IgG）的应用阻断了器械训练的保护作用。直接（鞘内）应用BDNF替代工具训练，以阻断学习缺陷的诱导和表达。不可控的刺激也会引起机械反应性（异常性疼痛）的增加，这也被BDNF阻止。TrkB-IgG阻断了器械训练的恢复作用，鞘内BDNF替代训练以逆转缺陷。总之，这些发现概述了BDNF在介导可控刺激对脊髓可塑性的有益作用中的关键作用。
Brain-derived neurotrophic factor (BDNF) has been characterized as a potent modulator of neural plasticity in both the brain and spinal cord. The present experiments use an in vivo model system to demonstrate that training with controllable stimulation increases spinal BDNF expression and engages a BDNF-dependent process that promotes adaptive plasticity. Spinally transected rats administered legshock whenever one hindlimb is extended (controllable stimulation) exhibit a progressive increase in flexion duration. This simple form of response-outcome (instrumental) learning is not observed when shock is given independent of leg position (uncontrollable stimulation). Uncontrollable electrical stimulation also induces a lasting effect that impairs learning for up to 48 hrs. Training with controllable shock can counter the adverse consequences of uncontrollable stimulation, to both prevent and reverse the learning deficit. Here it is shown that the protective and restorative effect of instrumental training depends on BDNF. Cellular assays showed that controllable stimulation increased BDNF mRNA expression and protein within the lumbar spinal cord. These changes were associated with an increase in the BDNF receptor TrkB protein within the dorsal horn. Evidence is then presented that these changes play a functional role in vivo. Application of a BDNF inhibitor (TrkB-IgG) blocked the protective effect of instrumental training. Direct (intrathecal) application of BDNF substituted for instrumental training to block both the induction and expression of the learning deficit. Uncontrollable stimulation also induced an increase in mechanical reactivity (allodynia) and this too was prevented by BDNF. TrkB-IgG blocked the restorative effect of instrumental training and intrathecal BDNF substituted for training to reverse the deficit. Taken together, these findings outline a critical role for BDNF in mediating the beneficial effects of controllable stimulation on spinal plasticity.
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DOI：
10.1111/j.1460-9568.2008.06524.x
发表时间：
2008-12
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Gomez-Pinilla F;Vaynman S;Ying Z
通讯作者：
Ying Z
影响因子：
2.7
作者：
Bigbee, Allison J.;Crown, Eric D.;Edgerton, V. Reggie
通讯作者：
Edgerton, V. Reggie
影响因子：
2.5
作者：
Crown, ED;Grau, JW
通讯作者：
Grau, JW
影响因子：
2.9
作者：
Crown, ED;Ferguson, AR;Grau, JW
通讯作者：
Grau, JW
影响因子：
1.9
作者：
Grau, JW;Barstow, DG;Joynes, RL
通讯作者：
Joynes, RL