Primary cilia are centriole-derived sensory organelles that are present in most mammalian cells, including astrocytes and neurons. Evidence is emerging that astrocyte and neuronal primary cilia demonstrate a dichotomy in the mature mouse brain. However, it is unknown how astrocytic and neuronal primary cilia change their morphology and ciliary proteins when exposed to reactive insults including epilepsy and traumatic brain injury. We used a double transgenic mouse strain (Arl13b-mCherry; Centrin2-GFP), in which we found spontaneous seizures, and a cortical injury model to examine the morphological changes of astrocytic and neuronal primary cilia under reactive conditions. Transgenic overexpression of Arl13b drastically increases the length of astrocytic and neuronal primary cilia in the hippocampus, as well as the cilia lengths of cultured astrocytes and neurons. Spontaneous seizures shorten Arl13b-positive astrocytic cilia and AC3-positive neuronal cilia in the hippocampus. In a cortical injury model, Arl13b is not detectable in primary cilia, but Arl13b protein relocates to the cell body and has robust expression in the proximity of injured tissues. In contrast, the number of AC3-positive cilia near injured tissues remains unchanged, but their lengths become shorter. These results on astrocytic cilia implicate Arl13b in regulating astrocyte proliferation and tissue regeneration, while the shortening of AC3-positive cilia suggests adaptive changes of neuronal primary cilia under excitotoxicity.

中文翻译：

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星形胶质细胞和神经原发性纤毛在反应性损伤下的形态变化各不相同。

原发纤毛是存在于大多数哺乳动物细胞（包括星形胶质细胞和神经元）中的源自中心粒的感觉细胞器。越来越多的证据表明，星形胶质细胞和神经原发性纤毛在成熟的小鼠大脑中表现出二分法。然而，未知的是星形胶质细胞和神经元初级纤毛在暴露于包括癫痫和脑外伤在内的反应性损伤时如何改变其形态和纤毛蛋白。我们使用了一种双转基因小鼠品系（Arl13b-mCherry; Centrin2-GFP），在其中我们发现了自发性癫痫发作，并使用了皮层损伤模型来检查在反应条件下星形细胞和神经原发性纤毛的形态变化。Arl13b的转基因过表达极大地增加了海马中星形细胞和神经元纤毛的长度，以及培养的星形胶质细胞和神经元的纤毛长度。自发性癫痫会缩短海马中Arl13b阳性星形胶质纤毛和AC3阳性神经元纤毛。在皮质损伤模型中，在原发纤毛中未检测到Arl13b，但Arl13b蛋白重新定位到细胞体，并在受损组织附近表达强健。相反，受损组织附近AC3阳性纤毛的数量保持不变，但其长度变短。这些关于星形细胞纤毛的结果暗示了Arl13b调节星形胶质细胞的增殖和组织再生，而AC3阳性纤毛的缩短表明在兴奋性毒性下神经元原发纤毛的适应性变化。在皮质损伤模型中，在原发纤毛中未检测到Arl13b，但Arl13b蛋白重新定位到细胞体，并在受损组织附近表达强健。相反，受损组织附近AC3阳性纤毛的数量保持不变，但其长度变短。这些关于星形细胞纤毛的结果暗示了Arl13b调节星形胶质细胞的增殖和组织再生，而AC3阳性纤毛的缩短表明在兴奋性毒性下神经元原发纤毛的适应性变化。在皮质损伤模型中，在原发纤毛中未检测到Arl13b，但Arl13b蛋白重新定位到细胞体，并在受损组织附近表达强健。相反，受损组织附近AC3阳性纤毛的数量保持不变，但其长度变短。这些关于星形细胞纤毛的结果暗示了Arl13b调节星形胶质细胞的增殖和组织再生，而AC3阳性纤毛的缩短表明在兴奋性毒性下神经元原发纤毛的适应性变化。