Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.
Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.
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DOI：
10.1371/journal.pone.0017176
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发表时间：
2011-03-03
期刊：
影响因子：
3.7
通讯作者：
Cheng JX
中科院分区：
文献类型：
--
作者：
Huff TB;Shi Y;Sun W;Wu W;Shi R;Cheng JX
高频电刺激正在成为治疗神经系统疾病的一种很有前途的疗法，但对中枢神经系统对刺激的反应仍知之甚少。本研究采用激光扫描相干反斯托克斯拉曼散射(CARS)技术实时检测活体脊髓组织中髓鞘对电刺激的反应。在200 Hz电刺激时，观察到兰维尔结节旁髓鞘回缩。回缩在刺激开始几分钟后开始，并在刺激停止后持续10分钟，但在2小时恢复期后被发现逆转。髓鞘回缩导致免疫荧光显示Kv1.2钾通道外露。因此，用钾通道阻滞剂4-氨基吡啶处理受刺激的组织，会在复合动作电位曲线上出现肩峰。髓鞘的无标记CARS成像和免疫标记蛋白在Ranvier结节的多光子荧光成像显示，高频刺激通过病理性钙离子内流到轴突，钙蛋白酶激活，以及通过血影蛋白分解细胞骨架而诱导结旁髓鞘收缩。
High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.
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谷氨酸兴奋性毒性导致节旁髓磷脂分裂和回缩。
影响因子：
3.7
作者：
Fu, Yan;Sun, Wenjing;Shi, Yunzhou;Shi, Riyi;Cheng, Ji-Xin
通讯作者：
Cheng, Ji-Xin
影响因子：
64.8
作者：
CHIU, SY;RITCHIE, JM
通讯作者：
RITCHIE, JM
DOI：
10.1098/rspb.1985.0037
发表时间：
1985-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BOWE, CM;KOCSIS, JD;WAXMAN, SG
通讯作者：
WAXMAN, SG
影响因子：
16.2
作者：
Mayberg, HS;Lozano, AM;Kennedy, SH
通讯作者：
Kennedy, SH
影响因子：
6
作者：
Kupsch, A;Kuehn, A;Trottenberg, T
通讯作者：
Trottenberg, T