Expression Profile of Histone Deacetylases in Patients with Hippocampal Sclerosis
31 July 2019 (online)
Introduction: Epigenetic mechanisms like altered histone acetylation may have a crucial role in epileptogenesis. Altered histone H3 and H4 acetylation has been demonstrated in experimental models of temporal lobe epilepsy (TLE). Epigenetic histone deacetylation inhibition prevents the development and persistence of TLE in animal models. This study was designed to investigate the changes in the expression of the histone deacetylases (HDACs) in the surgically resected tissue specimens of hippocampal sclerosis (HS) patients with the aim to decipher its role in epileptogenesis.
Methods: For this study, surgically resected tissue specimens of 23 patients were obtained. We have used histopathologically normal hippocampus tissues (17) obtained from the postmortem cases without any history of seizures or other neurological disorders as nonepileptic controls. mRNA levels of HDACs were evaluated by quantitative real-time PCR. HDAC activity and the levels of significantly altered HDACs were measured spectrophotometrically.
Results: A significant increase in mRNA level of HDAC1 (9.02 ± 2.97 fold, p = 0.029), HDAC4 (4.17 ± 1.23 fold, p = 0.046), HDAC5 (7.05 ± 2.40 fold, p = 0.036), HDAC6 (9.35 ± 2.35 fold, p = 0.017), HDAC10 (9.02 ± 2.97 fold, p = 0.021), and HDAC11 (4.10 ± 1.33 fold, p = 0.043) expression was observed in HS as compared with control. We did not observe any significant changes in the HDAC2, HDAC3, HDAC7, HDAC8, and HDAC9 levels in MTLE-HS when compared with control.
Conclusion: This is the first comprehensive study that demonstrated the significant changes in various HDACs in HS patients, providing a rationale for conducting further exploratory studies.