Rafiei Parisa, Mian Huda S, Iyer Shruthi H, Draves Samantha B, Matthews Stephanie A, Rendon Daniel E, Neesen Emma J, Dunlay Madeline, Revis McKenna, Glisan Adrianna L, Simeone Timothy A, Simeone Kristina A
Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA.
Nutrients. 2025 May 28;17(11):1824. doi: 10.3390/nu17111824.
Hyperexcitable neuronal activity associated with seizures may disrupt brain homeostasis resulting in abnormal glucose and nutrient management and metabolism. Specialized ependymal cells known as tanycytes line the third ventricle wall bridging communication between the brain, CSF, and blood. Despite their positional importance, whether tanycytes are impacted by epilepsy is unknown. Here, known protein markers of tanycytes were assessed in the -null mouse model of genetic epilepsy with spontaneous recurrent seizures (SRS mice). Further, whether an anti-seizure metabolic ketogenic diet (KD), previously proven effective in SRS mice, restored protein levels was determined. : Known tanycyte proteins, including glucose transporter 1 (GLUT1), glial fibrillary acidic protein (GFAP), and doublecortin (DCX, to determine potential neurogenic differences) were examined throughout the anterior-posterior axis of the third ventricle using immunofluorescent histochemistry. : Decreased GLUT1 immunoreactivity and elevated GFAP levels were found in the SRS cohorts. The number of neurogenic DCX-expressing cells did not differ. Two weeks of KD treatment reduced GFAP to WT levels. GLUT1 remained low in KD-treated SRS mice. : These data suggest that the expression of proteins important for the structure and function of tanycytes is altered in preclinical epilepsy and is differentially restored with KD treatment. Whether tanycytes actively participate in the pathophysiology of epilepsy or associated comorbidities is an intriguing possibility given their integral role in brain homeostasis.
与癫痫发作相关的神经元活动过度兴奋可能会破坏脑内稳态，导致葡萄糖和营养物质的管理及代谢异常。一种名为室管膜胶质细胞的特殊室管膜细胞排列在第三脑室壁上，在大脑、脑脊液和血液之间建立联系。尽管它们位置重要，但室管膜胶质细胞是否会受到癫痫的影响尚不清楚。在此，在具有自发性复发性癫痫发作的基因癫痫无效小鼠模型（SRS小鼠）中评估了室管膜胶质细胞已知的蛋白质标志物。此外，还确定了先前在SRS小鼠中被证明有效的抗癫痫生酮饮食（KD）是否能恢复蛋白质水平。：使用免疫荧光组织化学在第三脑室的前后轴上检查了已知的室管膜胶质细胞蛋白，包括葡萄糖转运蛋白1（GLUT1）、胶质纤维酸性蛋白（GFAP）和双皮质素（DCX，用于确定潜在的神经源性差异）。：在SRS队列中发现GLUT1免疫反应性降低，GFAP水平升高。表达神经源性DCX的细胞数量没有差异。两周的KD治疗使GFAP降至野生型水平。在接受KD治疗的SRS小鼠中，GLUT1仍然较低。：这些数据表明，在临床前癫痫中，对室管膜胶质细胞的结构和功能重要的蛋白质表达发生了改变，并且KD治疗能使其有差异地恢复。鉴于室管膜胶质细胞在脑内稳态中的不可或缺的作用，它们是否积极参与癫痫或相关合并症的病理生理学是一个有趣的可能性。
