Neuronal and astrocytic tetraploidy is increased in drug‐resistant epilepsy

• Published in: Neuropathology and applied neurobiology Vol. 49; no. 1; pp. e12873 - n/a
• Main Authors: Sanz‐García, Ancor, Sánchez‐Jiménez, Patricia, Granero‐Cremades, Inmaculada, Toledo, María, Pulido, Paloma, Navas, Marta, Frade, José María, Pereboom‐Maicas, Matilde Desirée, Torres‐Díaz, Cristina Virginia, Ovejero‐Benito, María C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.02.2023
• Subjects: Amygdala; Astrocytes; Astrocytes - pathology; Brain - pathology; Drug resistance; Epilepsy; Epilepsy - pathology; Epilepsy, Temporal Lobe - pathology; Flow cytometry; Hippocampus; Hippocampus - pathology; Humans; Mental disorders; neural cell cycle; Neurological diseases; Neurons; Neurons - pathology; polyploidy; refractory epilepsy; temporal lobe epilepsy; Tetraploidy; Tumor Suppressor Proteins; temporal lobe epilepsy; polyploidy; refractory epilepsy; neural cell cycle; tetraploidy; flow cytometry; astrocytes
• ISSN: 0305-1846; 1365-2990; 1365-2990
• DOI: 10.1111/nan.12873

Aims Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug‐resistant. The exact aetiology of drug‐resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. Methods For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post‐mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. Results The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100β) followed by flow cytometry analysis. The 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. 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 analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. Conclusions We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment. We demonstrated the existence of tetraploid astrocytes in healthy human brain. Neural tetraploidy is increased in drug resistant epilepsy patients hippocampus. Astrocytic tetraploidy is higher in drug resistant epilepsy patients hippocampus.