Bazzurro Virginia, Gatta Elena, Angeli Elena, Cupello Aroldo, Lange Stefan, Jennische Eva, Robello Mauro, Diaspro Alberto
DIFILAB, Department of Physics, University of Genoa, Italy.
Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Sweden.
IBRO Neurosci Rep. 2024 Aug 5;17:188-195. doi: 10.1016/j.ibneur.2024.08.001. eCollection 2024 Dec.
The Antisecretory Factor (AF) is a protein that can reduce intestinal hypersecretion and various inflammation disorders . Discovered in many mammalian tissues and plasma, its mechanism of action remains unknown. Interestingly, its induction has been found to counteract vertigo in patients with Méniere's disease. This suggests an inherent ability to control body balance and posture, an activity that may play a role in cerebellar function. Therefore, it may be worthwhile to investigate whether this activity can inhibit neuronal cells involved in cerebellar circuitries and its potential action on enteric nervous system ganglia, which could explain its antisecretory effect in the intestine. Previously, we studied the role of AF on GABA receptors in cerebellar granule cells, taking advantage of electrophysiology and evaluating the effects of the administration of AF-16, an AF peptide. Treatment with AF-16 increased GABA receptor responses, especially those containing the α subunit. Here, we performed immunofluorescence experiments by staining α and α subunits before and after incubation with AF-16, analyzed super-resolved images comparing pre- and post-treatment maps and critically examined these experimental results with our previous electrophysiological data to shed light on the mechanisms of action of AF protein on GABA receptor subpopulations, specifically the "fast" receptors of α β γ composition that contain either the α or the α subunit. The results indicate that the α subunit is redistributed, with a decrease in neurites and an increase in soma. Conversely, the α subunit shows opposite results, with an increase in neurites and a decrease in soma.
抗分泌因子(AF)是一种能够减少肠道分泌亢进和各种炎症性疾病的蛋白质。它在许多哺乳动物组织和血浆中被发现,但其作用机制尚不清楚。有趣的是,已发现它的诱导可抵消梅尼埃病患者的眩晕。这表明它具有控制身体平衡和姿势的内在能力,这种活动可能在小脑功能中发挥作用。因此,研究这种活动是否能抑制参与小脑回路的神经元细胞及其对肠神经系统神经节的潜在作用可能是值得的,这可以解释它在肠道中的抗分泌作用。此前,我们利用电生理学研究了AF对小脑颗粒细胞中GABA受体的作用,并评估了AF肽AF - 16给药的效果。用AF - 16处理可增加GABA受体反应,尤其是含有α亚基的反应。在此,我们通过在与AF - 16孵育前后对α和α亚基进行染色来进行免疫荧光实验,分析超分辨图像并比较处理前后的图谱,并结合我们之前的电生理数据对这些实验结果进行严格审查,以阐明AF蛋白对GABA受体亚群的作用机制,特别是由αβγ组成且含有α或α亚基的“快速”受体。结果表明,α亚基重新分布,神经突减少而胞体增加。相反,α亚基显示出相反的结果,神经突增加而胞体减少。