Chronic defects in intraspinal mechanisms of spike encoding by spinal motoneurons following chemotherapy.
Chronic defects in intraspinal mechanisms of spike encoding by spinal motoneurons following chemotherapy.
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DOI：
10.1016/j.expneurol.2020.113354
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发表时间：
2020-09
影响因子：
5.3
通讯作者：
Cope TC
中科院分区：
文献类型：
--
作者：
Housley SN;Nardelli P;Powers RK;Rich MM;Cope TC
化疗引起的感觉运动障碍，包括步态和平衡障碍，以及身体疲劳通常持续数月，有时甚至数年，直至癌症无病生存。虽然与感觉功能受损有关，但慢性感觉运动障碍也可能取决于化疗引起的其他神经元类型的缺陷。在这份报告中，我们将考虑运动神经元，如果长期受损，必然会降低运动行为。本研究旨在确定运动神经元是否有资格作为独立于感觉障碍的慢性感觉运动障碍的候选因素。我们在大鼠体内测试了这种可能性，5周后，人类规模的治疗与铂为基础的化合物之一，奥沙利铂，广泛用于各种癌症的化疗。测量脊髓运动神经元对不同固定水平的电极电流注入的动作电位放电，以评估神经元对刺激编码的内在能力。在未治疗对照大鼠中证实的刺激持续时间和强度编码在奥沙利铂治疗大鼠中严重退化，其中运动神经元总是表现出不稳定的放电，从一个刺激试验到下一个刺激试验是不持续的、不可预测的，并且对电流强度的变化无反应。结合计算机建模的膜电压的峰间振荡的直接测量指出，亚阈值电导的畸变作为一个合理的贡献者受损的射击行为。这些研究结果验证了受损的尖峰编码作为候选贡献者，在运动神经元的情况下，在流动性和疲劳的赤字。异常放电也成为值得在其他CNS神经元中测试的缺陷，作为患者化疗诱导的感知和认知障碍的潜在贡献者。
Chemotherapy-induced sensorimotor disabilities, including gait and balance disorders, as well as physical fatigue often persist for months and sometimes years into disease free survival from cancer. While associated with impaired sensory function, chronic sensorimotor disorders might also depend on chemotherapy-induced defects in other neuron types. In this report, we extend consideration to motoneurons, which, if chronically impaired, would necessarily degrade movement behavior. The present study was undertaken to determine whether motoneurons qualify as candidate contributors to chronic sensorimotor disability independently from sensory impairment. We tested this possibility in vivo from rats 5 weeks following human-scaled treatment with one of the platinum-based compounds, oxaliplatin, widely used in chemotherapy for a variety of cancers. Action potential firing of spinal motoneurons responding to different fixed levels of electrode-current injection was measured in order to assess the neurons’ intrinsic capacity for stimulus encoding. The encoding of stimulus duration and intensity corroborated in untreated control rats was severely degraded in oxaliplatin treated rats, in which motoneurons invariably exhibited erratic firing that was unsustained, unpredictabl e from one stimulus trial to the next, and unresponsive to changes in current strength. Direct measurements of interspike oscillations in membrane voltage combined with computer modeling pointed to aberrations in subthreshold conductances as a plausible contributor to impaired firing behavior. These findings authenticate impaired spike encoding as a candidate contributor to, in the case of motoneurons, deficits in mobility and fatigue. Aberrant firing also becomes a deficit worthy of testing in other CNS neurons as a potential contributor to perceptual and cognitive disorders induced by chemotherapy in patients.
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影响因子：
4.5
作者：
Chatelier, Aurelien;Zhao, Juan;Chahine, Mohamed
通讯作者：
Chahine, Mohamed
DOI：
10.1016/j.jchromb.2003.08.049
发表时间：
2003-12-05
影响因子：
3
作者：
Guo, P;Ma, JG;Gallo, JM
通讯作者：
Gallo, JM
影响因子：
3.3
作者：
Destexhe, A;Rudolph, M;Sejnowski, TJ
通讯作者：
Sejnowski, TJ
影响因子：
11.4
作者：
Areti A;Yerra VG;Naidu V;Kumar A
通讯作者：
Kumar A
影响因子：
2.4
作者：
Briones TL;Woods J
通讯作者：
Woods J