P. Rafiei, HS. Mian, SH. Iyer, SB. Draves, SA. Matthews, DE. Rendon, EJ. Neesen, M. Dunlay, M. Revis, AL. Glisan, TA. Simeone, et al. (2025). In Preclinical Epilepsy, GLUT1 and GFAP Dysregulation in Cells Surrounding the Third Ventricle, Including Tanycytes, Is Differentially Restored with Ketogenic Diet Treatment. Nutrients, 17(11). https://doi.org/10.3390/nu17111824

PubMed 40507093

[Abstract]
Background/Objectives: 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 Kcna1-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. Methods: 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. Results: 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. Conclusions: 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.