Filipi Tereza, Tureckova Jana, Vanatko Ondrej, Chmelova Martina, Kubiskova Monika, Sirotova Natalia, Matejkova Stanislava, Vargova Lydia, Anderova Miroslava
Department of Cellular Neurophysiology, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czechia.
Second Faculty of Medicine, Charles University, Prague, Czechia.
Front Cell Neurosci. 2024 Oct 10;18:1472374. doi: 10.3389/fncel.2024.1472374. eCollection 2024.
Astrocytes are crucial for the functioning of the nervous system as they maintain the ion homeostasis via volume regulation. Pathological states, such as amyotrophic lateral sclerosis (ALS), affect astrocytes and might even cause a loss of such functions. In this study, we examined astrocytic swelling/volume recovery in both the brain and spinal cord of the SOD1 animal model to determine the level of their impairment caused by the ALS-like pathology. Astrocyte volume changes were measured in acute brain or spinal cord slices during and after exposure to hyperkalemia. We then compared the results with alterations of extracellular space (ECS) diffusion parameters, morphological changes, expression of the Kir4.1 channel and the potassium concentration measured in the cerebrospinal fluid, to further disclose the link between potassium and astrocytes in the ALS-like pathology. Morphological analysis revealed astrogliosis in both the motor cortex and the ventral horns of the SOD1 spinal cord. The activated morphology of SOD1 spinal astrocytes was associated with the results from volume measurements, which showed decreased swelling of these cells during hyperkalemia. Furthermore, we observed lower shrinkage of ECS in the SOD1 spinal ventral horns. Immunohistochemical analysis then confirmed decreased expression of the Kir4.1 channel in the SOD1 spinal cord, which corresponded with the diminished volume regulation. Despite astrogliosis, cortical astrocytes in SOD1 mice did not show alterations in swelling nor changes in Kir4.1 expression, and we did not identify significant changes in ECS parameters. Moreover, the potassium level in the cerebrospinal fluid did not deviate from the physiological concentration. The results we obtained thus suggest that ALS-like pathology causes impaired potassium uptake associated with Kir4.1 downregulation in the spinal astrocytes, but based on our data from the cortex, the functional impairment seems to be independent of the morphological state.
星形胶质细胞对神经系统的功能至关重要，因为它们通过体积调节来维持离子稳态。诸如肌萎缩侧索硬化症（ALS）等病理状态会影响星形胶质细胞，甚至可能导致此类功能丧失。在本研究中，我们检测了SOD1动物模型脑和脊髓中星形胶质细胞的肿胀/体积恢复情况，以确定由ALS样病理导致的损伤程度。在急性脑或脊髓切片中，于暴露于高钾血症期间及之后测量星形胶质细胞的体积变化。然后，我们将结果与细胞外间隙（ECS）扩散参数的改变、形态变化、Kir4.1通道的表达以及脑脊液中测量的钾浓度进行比较，以进一步揭示ALS样病理中钾与星形胶质细胞之间的联系。形态学分析显示，SOD1脊髓的运动皮层和腹角均存在星形胶质细胞增生。SOD1脊髓星形胶质细胞的活化形态与体积测量结果相关，该结果显示这些细胞在高钾血症期间肿胀减少。此外，我们观察到SOD1脊髓腹角中ECS的收缩较低。免疫组织化学分析随后证实SOD1脊髓中Kir4.1通道的表达降低，这与体积调节减弱相对应。尽管存在星形胶质细胞增生，但SOD1小鼠的皮层星形胶质细胞在肿胀方面未显示改变，Kir4.1表达也未发生变化，并且我们未发现ECS参数有显著变化。此外，脑脊液中的钾水平未偏离生理浓度。因此，我们获得的结果表明，ALS样病理导致脊髓星形胶质细胞中与Kir4.1下调相关的钾摄取受损，但基于我们从皮层获得的数据，功能损伤似乎与形态状态无关。
