Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold
Circuit reconstruction of newborn neurons after spinal cord injury in adult rats via an NT3-chitosan scaffold
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通过 NT3-壳聚糖支架重建成年大鼠脊髓损伤后新生神经元的回路
DOI：
10.1016/j.pneurobio.2022.102375
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发表时间：
2022-11-24
影响因子：
6.7
通讯作者：
Yang，Zhaoyang
中科院分区：
文献类型：
--
作者：
Wang，Zijue;Duan，Hongmei;Yang，Zhaoyang
植入的神经营养素-3（NT 3）-壳聚糖支架可以募集内源性神经干细胞迁移到损伤区域并在成人脊髓损伤（SCI）后分化为成熟神经元。然而，这些新生神经元的身份以及它们是否可以形成功能性突触和回路以促进截瘫后的恢复仍然未知。通过结合先进的技术，我们揭示了几种亚型的新生神经元接受来自皮质脊髓束（CST），红核脊髓束（CST）和脊髓上束的突触输入。它们在受伤的脊髓区域形成了一个功能性神经回路，进一步驱动病变下方的局部回路。我们的结果表明，NT 3-壳聚糖支架促进脊髓神经元的成熟和脊髓神经回路的重建在损伤后12周的损伤区域。跨突触病毒实验表明，这些新生的脊髓神经元接受来自CST和ESTA的突触连接，并通过新形成的突触驱动病变下方的神经回路。这些重建的回路成功地恢复了病变脊髓节段下方神经肌肉接头（NMJ）的形成和功能。这些发现表明，NT 3-壳聚糖支架促进中继神经回路的形成，以适应各种类型的大脑下行输入，并促进截瘫后的功能恢复。
An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts. They formed a functional neural circuit at the injured spinal region, further driving the local circuits beneath the lesion. Our results showed that the NT3-chitosan scaffold facilitated the maturation of spinal neurons and the reestablishment of the spinal neural circuit in the lesion region 12 weeks after SCI. Transsynaptic virus experiments revealed that these newborn spinal neurons received synaptic connections from the CST and RST and drove the neural circuit beneath the lesion via newly formed synapses. These re-established circuits successfully recovered the formation and function of the neuromuscular junction (NMJ) beneath the lesion spinal segments. These findings suggest that the NT3-chitosan scaffold promotes the formation of relay neural circuits to accommodate various types of brain descending inputs and facilitate functional recovery after paraplegia.