584 - Expression of Glucose Transporters and Neuronal Trophic Factors in Focal Cortical Dysplasia

Publication Number: 3565.584

Lisa Soumekh, Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, Los Angeles, CA, United States; Nicole Anderson, Stanford University School of Medicine, Santa Cruz, CA, United States; Bo-Chul Shin, UCLA Mattel Childrens Hospital, Los Angeles, CA, United States; Aria Fallah, UCLA, Los Angeles, CA, United States; Sherin U.. Devaskar, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA, United States

Background: Focal cortical dysplasia (FCD) presents as a drug-resistant epilepsy during childhood that reflects an aberrancy in cortical development. FCD is localized by aberrant EEG mapping revealing hyperexcitability and PET scans that detect perturbed neurovascular glucose metabolism. We hypothesize that changes in localized glucose transporters and in neuronal trophic factors may underlie these key changes in FCD.

Objective: To test this hypothesis, we quantified major brain glucose transporters (GLUT1 and GLUT3), and neuronal trophic factors (BDNF and β-tubulin).

Design/Methods: Clinically indicated and neuro-surgically resected human brain tissues (n=17) were retrieved from the UCLA Biobank under an IRB approved protocol. All included tissues were characterized by the histopathological ILAE classification for FCD subtypes 1c (n=9) or 2a (n=8). Control pediatric brain tissue was obtained from the NIH NeuroBiobank (n=3). These tissues were subjected to western blot analysis using anti-GLUT1, anti-GLUT3, anti-BDNF and anti-β tubulin III antibodies with vinculin as an internal control. Comparisons of the protein band densities were validated by an unpaired t-test or ANOVA. A p-value < 0.05 was considered significant.

Results: In this pilot study, we noted no significant difference in GLUT1 between control and all FCD subtypes, although FCD notably had lower expression rates (mean ± SEM: 100 ± 35.77 vs 68.28 ± 8.277, p=0.20). No difference was observed between control vs. FCD type 1 (p=0.54), control vs. FCD type 2 (p=0.60), or FCD type 1 vs. FCD type 2 (p=0.99). There was also no difference in GLUT3 expression between control and all FCD subtypes (100 ± 22.61 vs. 93.42 ± 8.102, p=0.76). No difference was observed between control vs. FCD type 1 (p=0.99), control vs. FCD type 2 (p=0.99), or FCD type 1 vs FCD type 2 (p=0.99). Similarly, there was no significant difference in expression of BDNF (p=0.31) and β-tubulin (p=0.97) between controls and FCD subtypes.

Conclusion(s): In this rare disorder, our study was limited by a small sample size which bears somatic mutations of genes within various pathways. While attempts at obtaining more samples is underway, the lack of differences in GLUT1, GLUT3, BDNF and β-tubulin suggests a need to explore additional GLUT isoforms and neuronal growth factors. Insights gained from these studies may form the basis for a non-invasive genetic or proteomic panel and allow for early diagnosis. A more immediate diagnosis would lead to early interventions and consequently, the prevention of symptoms that have life altering outcomes for children diagnosed with FCD.

Figure 1
Protein quantification of (A) Glut 1 and (B) Glut 3 as percent of control protein concentration