Proportions of four distinct classes of sensory neurons are retained even when axon regeneration is enhanced following peripheral nerve injury.

Proportions of four distinct classes of sensory neurons are retained even when axon regeneration is enhanced following peripheral nerve injury.
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DOI:
10.3389/fnana.2023.1303888
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发表时间:
2023
影响因子:
2.9
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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周围神经损伤的恢复很差,因为轴突再生缓慢且效率低下。通过其TrkB受体或通过其下游效应器增加神经元脑源性神经营养因子(BDNF)信号传导的实验疗法增强轴突再生,增加运动和感觉神经元的数量,其轴突成功再生并重新支配肌肉靶点。本研究的目的是比较四种不同类型的感觉(背根神经节,DRG)神经元的比例,成功地再神经支配两个不同的肌肉目标在对照小鼠和小鼠治疗的神经元,以增强轴突再生。在坐骨神经切断和修复后,C57 BL/6 J小鼠用R13(释放小分子TrkB配体7,8-二羟基黄酮的前药)和化合物11(CP 11)(天冬酰胺酰内肽酶(δ-分泌酶)的抑制剂)或对照载体处理2周。损伤后4周,将不同的荧光逆行示踪剂注射到腓肠肌和胫骨前肌中,以标记成功地使这些肌肉重新神经支配的DRG神经元。使用免疫荧光,逆行标记的DRG神经元也表达四种不同的感觉神经元类的标记物进行计数。R13或CP 11治疗导致肌肉神经再支配的DRG神经元比vehicletreated对照组多得多,但神经元表达蛋白质与不同类别的DRG神经元研究在很大程度上是在相同的比例发现在完整的小鼠。
Recovery from peripheral nerve injuries is poor because axon regeneration is slow and inefficient. Experimental therapies that increase signaling of neuronal brain-derived neurotrophic factor (BDNF) through its TrkB receptor or through its downstream effectors enhance axon regeneration, increasing the number of motor and sensory neurons whose axons successfully regenerate and reinnervate muscle targets. The goal of this study was to compare the proportions of four different classes of sensory (dorsal root ganglion, DRG) neurons that successfully reinnervate two different muscle targets in control mice and mice treated pharmacologically to enhance axon regeneration. Following sciatic nerve transection and repair, C57BL/6 J mice were treated for 2 weeks, either with R13, a prodrug that releases the small molecule TrkB ligand, 7,8-dihydroxyflavone, with compound 11 (CP11), an inhibitor of asparaginyl endopeptidase (δ-secretase), or with a control vehicle. Four weeks after injury, different fluorescent retrograde tracers were injected into the gastrocnemius and tibialis anterior muscles to mark DRG neurons that had successfully reinnervated these muscles. Using immunofluorescence, retrogradely labeled DRG neurons also expressing markers of four different sensory neuronal classes were counted. Treatments with R13 or CP11 resulted in muscle reinnervation by many more DRG neurons than vehicletreated controls, but neurons expressing proteins associated with the different classes of DRG neurons studied were largely in the same proportions found in intact mice.
轴突损伤后独特的周围感觉神经元亚型的转录重编程。
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