Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury.
Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury.
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通过完全脊髓损伤的小鼠的非侵蚀性AAV介导的对前脊髓神经元的操纵改善后肢运动功能。
DOI：
10.1038/s41467-021-20980-4
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发表时间：
2021-02-03
影响因子：
16.6
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Brommer B;He M;Zhang Z;Yang Z;Page JC;Su J;Zhang Y;Zhu J;Gouy E;Tang J;Williams P;Dai W;Wang Q;Solinsky R;Chen B;He Z
完全性脊髓损伤（SCI）后，病变部位以下的脊髓节段通过椎管内固有脊髓网络保持节段间的通讯。然而，目前尚不清楚是否有选择性地操纵这些回路可以恢复运动功能，在缺乏大脑来源的输入。通过利用SCI后受损的血-脊髓屏障，我们优化了一组程序，其中通过尾静脉给予AAV 9载体有效地抑制成年小鼠胸部挤压伤后病变相邻脊髓节段中的神经元。通过这种方法，我们使用化学致动器来改变具有完全胸部挤压伤的成年小鼠胸髓中固有脊髓神经元的兴奋性。我们发现，激活这些胸部神经元，使一致的和显着的后肢步进改善，而直接操纵的神经元在腰脊髓导致肌肉痉挛没有意义的运动。引人注目的是，操纵胸部水平的兴奋性或抑制性本体脊髓神经元会导致不同的行为结果，对站立或踏步产生优先影响，这是运动功能的两个关键要素。这些结果证明了一种策略，使胸部固有脊髓神经元，以改善后肢功能，并提供见解，优化神经调制为基础的战略，治疗脊髓损伤。完全性脊髓损伤后，病变部位以下的脊髓节段通过椎管内固有脊髓网络保持节段间的联系。在这里，作者表明，这些回路中的神经元可以通过化学遗传学调节来改善脊髓损伤后小鼠的运动功能。
After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI. After complete spinal cord injury, spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. Here, the authors show that neurons in these circuits can be chemogenetically modulated to improve locomotor function in mice after spinal cord injury.
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DOI：
10.1523/jneurosci.2973-12.2013
发表时间：
2013-03-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Deng LX;Deng P;Ruan Y;Xu ZC;Liu NK;Wen X;Smith GM;Xu XM
通讯作者：
Xu XM
DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
2.5
作者：
Gerasimenko, Yury;Gorodnichev, Ruslan;Edgerton, V. Reggie
通讯作者：
Edgerton, V. Reggie
影响因子：
4.2
作者：
Figley, Sarah A.;Khosravi, Ramak;Fehlings, Michael G.
通讯作者：
Fehlings, Michael G.
影响因子：
2.5
作者：
CHUNG, KS;COGGESHALL, RE
通讯作者：
COGGESHALL, RE