Preservation of KCC2 expression in axotomized abducens motoneurons and its enhancement by VEGF.
Preservation of KCC2 expression in axotomized abducens motoneurons and its enhancement by VEGF.
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DOI：
10.1007/s00429-023-02635-w
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发表时间：
2023-05
影响因子：
3.1
通讯作者：
Alvarez, Francisco J.
中科院分区：
文献类型：
--
作者：
Calvo, Paula M.;de la Cruz, Rosa R.;Pastor, Angel M.;Alvarez, Francisco J.
氯化钾协同转运蛋白2（KCC2）是神经元中主要的Cl−输出者。KCC2水平的任何改变都会导致Cl−稳态的变化，从而导致GABA或甘氨酸介导的抑制性突触电位的极性和振幅的变化。轴突切断下调KCC2在许多不同的运动神经元，它被怀疑，中断肌肉衍生的因子维持运动神经元KCC2的表达是部分负责。在这里，我们表明，KCC2的表达在所有的猫和大鼠的眼神经核，但同时trophilar和oculcerebral运动神经元下调KCC2轴突切断后，表达是不变的外展运动神经元。外源性应用血管内皮生长因子（VEGF），在肌肉中表达的神经营养因子，上调KCC2在轴突切断外展神经运动神经元以上的控制水平。与此同时，一项使用长期植入电极的猫记录清醒动物外展肌运动神经元的生理学研究表明，与VEGF治疗的轴突切断的外展肌运动神经元中的偏离固定和偏离定向扫视相关的抑制性输入显著高于对照组，但与眼睛相关的兴奋性信号在方向上没有变化。这是第一份关于运动神经元损伤后缺乏KCC2调节的报告，提出了VEGF在KCC2调节中的作用，并证明了清醒行为动物中KCC2和突触抑制之间的联系。
The potassium chloride cotransporter 2 (KCC2) is the main Cl− extruder in neurons. Any alteration in KCC2 levels leads to changes in Cl− homeostasis and, consequently, in the polarity and amplitude of inhibitory synaptic potentials mediated by GABA or glycine. Axotomy downregulates KCC2 in many different motoneurons and it is suspected that interruption of muscle-derived factors maintaining motoneuron KCC2 expression is in part responsible. In here, we demonstrate that KCC2 is expressed in all oculomotor nuclei of cat and rat, but while trochlear and oculomotor motoneurons downregulate KCC2 after axotomy, expression is unaltered in abducens motoneurons. Exogenous application of vascular endothelial growth factor (VEGF), a neurotrophic factor expressed in muscle, upregulated KCC2 in axotomized abducens motoneurons above control levels. In parallel, a physiological study using cats chronically implanted with electrodes for recording abducens motoneurons in awake animals, demonstrated that inhibitory inputs related to off-fixations and off-directed saccades in VEGF-treated axotomized abducens motoneurons were significantly higher than in control, but eye-related excitatory signals in the on direction were unchanged. This is the first report of lack of KCC2 regulation in a motoneuron type after injury, proposing a role for VEGF in KCC2 regulation and demonstrating the link between KCC2 and synaptic inhibition in awake, behaving animals.
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影响因子：
5.3
作者：
Chamma I;Chevy Q;Poncer JC;Lévi S
通讯作者：
Lévi S
影响因子：
5.3
作者：
Calvo, Paula M.;de la Cruz, Rosa R.;Pastor, Angel M.
通讯作者：
Pastor, Angel M.
影响因子：
5.3
作者：
Davis-Lopez de Carrizosa, Maria A.;Morado-Diaz, Camilo J.;Pastor, Angel M.
通讯作者：
Pastor, Angel M.
影响因子：
5.3
作者：
de Carrizosa, Maria A. Davis-Lopez;Morado-Diaz, Camilo J.;Pastor, Angel M.
通讯作者：
Pastor, Angel M.
影响因子：
5.5
作者：
ESCUDERO, M;DELACRUZ, RR;DELGADOGARCIA, JM
通讯作者：
DELGADOGARCIA, JM