Calcium homeostasis in parvalbumin DRG neurons is altered after sciatic nerve crush and sciatic nerve transection injuries.
Calcium homeostasis in parvalbumin DRG neurons is altered after sciatic nerve crush and sciatic nerve transection injuries.
复制标题
坐骨神经挤压和坐骨神经横断损伤后，小白蛋白 DRG 神经元的钙稳态发生改变。
DOI：
10.1152/jn.00707.2020
复制
发表时间：
2021
影响因子：
2.5
通讯作者：
Ladle,DavidR
中科院分区：
文献类型：
--
作者：
Walters,MarieC;Ladle,DavidR
周围神经损伤（PNI）后本体感觉神经元介导的反射异常可能限制功能改善，使患者残疾，影响其生活质量。我们研究了伤后钙瞬变的背根神经节（DRG）神经元的一个亚群，主要由本体感受器，以确定是否存在钙稳态的改变本体感受器，已记录在其他DRG神经元PNI后。使用转基因小鼠，我们限制表达的钙指标GCaMP 6s的DRG神经元含有小清蛋白（PV）。将两种性别的小鼠随机分配至假手术、坐骨神经挤压或坐骨神经横断和再缝合条件。在三个术后时间点之一（1-3天、7-11天和恢复后60天），从动物的离体制备物中记录钙瞬变。结果表明，PNI后PV DRG神经元的钙瞬变与假手术相比有显著差异。在对损伤的急性反应期间（1-3天）不存在短暂性恢复，但在恢复阶段（7-11天），认为轴突再生正在进行中，短暂性恢复与假手术显著不同。在后期恢复（伤后60天），在横断动物钙瞬变的衰减时间过程中的干扰持续存在，而从挤压动物的瞬变参数恢复正常。这些发现确定了本体感受神经元中钙稳态的缺陷，这可能导致PNI后本体感受反射未能完全恢复。显着差异的钙瞬变的粉碎与横断动物后，再支配说明钙稳态的改变是独特的损伤type.NEW & NOTEWORTHThis研究探讨钙稳态后，周围神经损伤后，背根神经节（DRG）神经元表达小白蛋白，一组大直径传入主要由本体感受器，使用双光子钙成像在完整的DRG。我们的研究结果确定了异常钙稳态作为周围神经损伤后感觉神经元功能障碍的另一个来源，揭示了两种损伤模型之间的差异，并跟踪这些变化如何在恢复过程中发展和解决。
Reflex abnormalities mediated by proprioceptive sensory neurons after peripheral nerve injury (PNI) can limit functional improvement, leaving patients with disability that affects their quality of life. We examined postinjury calcium transients in a subpopulation of dorsal root ganglion (DRG) neurons consisting primarily of proprioceptors to determine whether alterations in calcium homeostasis are present in proprioceptors, as has been documented in other DRG neurons after PNI. Using transgenic mice, we restricted expression of the calcium indicator GCaMP6s to DRG neurons containing parvalbumin (PV). Mice of both sexes were randomly assigned to sham, sciatic nerve crush, or sciatic nerve transection and resuture conditions. Calcium transients were recorded from ex vivo preparations of animals at one of three postsurgery time points: 1–3 days, 7–11 days, and after 60 days of recovery. Results demonstrated that the post-PNI calcium transients of PV DRG neurons are significantly different than sham. Abnormalities were not present during the acute response to injury (1–3 days), but transients were significantly different than sham at the recovery stage where axon regeneration is thought to be underway (7–11 days). During late-stage recovery (60 days postinjury), disturbances in the decay time course of calcium transients in transection animals persisted, whereas parameters of transients from crush animals returned to normal. These findings identify a deficit in calcium homeostasis in proprioceptive neurons, which may contribute to the failure to fully recover proprioceptive reflexes after PNI. Significant differences in the calcium transients of crush versus transection animals after reinnervation illustrate calcium homeostasis alterations are distinctive to injury type.NEW & NOTEWORTHYThis study examines calcium homeostasis after peripheral nerve injury in dorsal root ganglion (DRG) neurons expressing parvalbumin, a group of large-diameter afferents primarily consisting of proprioceptors, using two-photon calcium imaging in the intact DRG. Our findings identify aberrant calcium homeostasis as an additional source of sensory neuron dysfunction following peripheral nerve injury, uncover differences between two injury models, and track how these changes develop and resolve over the course of recovery.