NEURONAL AND ASTROCYTIC TETRAPLOIDY IS INCREASED IN DRUG-RESISTANT EPILEPSY

ABSTRACT Background Epilepsy is one of the most prevalent neurological diseases, a third of patients remain drug-resistant. The exact etiology of drug-resistant epilepsy (DRE) is still unknown. Neural tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. Materials & methods Cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Postmortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases were used as controls. The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100β) followed by flow cytometry analysis. Results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. Results A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analyzed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p=0.020) and astrocytes (p=0.002) in the hippocampus compared to controls. These results were validated by image cytometry. Conclusion We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects and increased levels of both cell types in DRE patients. This is the first time that tetraploid astrocytes are described in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.