Cranial irradiation induces axon initial segment dysfunction and neuronal injury in the prefrontal cortex and impairs hippocampal coupling.
Cranial irradiation induces axon initial segment dysfunction and neuronal injury in the prefrontal cortex and impairs hippocampal coupling.
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颅脑照射会引起轴突起始段功能障碍和前额皮质神经元损伤，并损害海马耦合。
DOI：
10.1093/noajnl/vdaa058
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Grosshans,DavidR
中科院分区：
文献类型：
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作者：
Zhang,Die;Zhou,Wei;Lam,ThanhThai;Li,Yan;Duman,JosephG;Dougherty,PatrickM;Grosshans,DavidR
背景脑肿瘤放射治疗常导致认知功能障碍。前额叶皮质(PFC)对于一系列不同的认知过程是至关重要的，然而，它在辐射引起的认知功能障碍中的作用尚不清楚。我们先前发现，颅脑照射损害了沿海马-PFC通路的神经可塑性。因此，我们假设脑照射直接影响PFC神经元的放电特性，从而导致神经元功能的缺失。方法采用活体记录的方法，监测SD大鼠颅脑照射后PFC神经元的放电活动和PFC和海马CA1/亚区的局部场电位。结果辐射后3d，PFC神经元的兴奋性增强，且兴奋性增强的时间与AISS的延长时间一致。在2周时，兴奋水平恢复到接近正常的水平，但自发放电的神经元数量减少。虽然PFC内NeuN阳性神经元的数量没有差异，但在2周时就出现了持续性神经元损伤，表现为ATF-3染色。辐射还扰乱了沿海马体-PFC通路的通讯，延长了区域之间的相位延迟。双脉冲比率分析表明，这是继发于突触前功能障碍。结论颅脑照射刺激和损伤存活的PFC神经元，并与部分阻断PFC与海马区的功能耦合有关。PFC的这些缺陷可能与辐射引起的认知功能障碍有关。
BackgroundRadiation therapy for brain tumors commonly induces cognitive dysfunction. The prefrontal cortex (PFC) is crucial for a diverse array of cognitive processes, however, its role in radiation-induced cognitive dysfunction is unknown. We previously found that cranial irradiation impairs neuroplasticity along the hippocampal–PFC pathway. Herein, we hypothesized that brain irradiation directly affects the firing properties of PFC neurons, contributing to deficits in neuronal functions.MethodsIn vivo recordings were used to monitor the firing activities of PFC neurons and local field potentials in both PFC and hippocampal CA1/subicular regions after cranial irradiation of Sprague Dawley rats. We further assessed the impacts of irradiation on axon initial segments (AISs) with immunofluorescence assays of PFC slices.ResultsWe found that PFC neurons exhibited increased excitation 3 days after radiation and the timing of increased excitation coincided with elongation of the AIS. At 2 weeks, excitation levels returned to nearly normal levels however the population of spontaneously firing neurons decreased. While the number of NeuN-positive neurons in the PFC was not different, persistent neuronal injury, manifested as ATF-3 staining, was present at 2 weeks. Radiation also disrupted communication along the hippocampal–PFC pathway, with elongation of the phase lag between regions. Analysis of paired-pulse ratios suggested that this was secondary to presynaptic dysfunction.ConclusionsCranial irradiation excited and injured surviving PFC neurons and was associated with a partial block of PFC’s functional coupling to the hippocampus. These deficits in the PFC may contribute to radiation-induced cognitive dysfunction.