# In Preclinical Epilepsy, GLUT1 and GFAP Dysregulation in Cells Surrounding the Third Ventricle, Including Tanycytes, Is Differentially Restored with Ketogenic Diet Treatment

## TL;DR

This study finds that proteins in tanycytes, cells near the third ventricle, are disrupted in a mouse model of epilepsy and partially restored by a ketogenic diet.

## Contribution

The study reveals differential restoration of GLUT1 and GFAP in tanycytes surrounding the third ventricle in an epilepsy model following ketogenic diet treatment.

## Key findings

- SRS mice showed decreased GLUT1 and elevated GFAP in third ventricle tanycytes.
- Ketogenic diet restored GFAP to wild-type levels but not GLUT1.
- Neurogenic DCX-expressing cell numbers were unchanged in SRS mice.

## 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.