Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug-resistant temporal lobe epilepsy and comorbid depression

LUCIANA D' ALESSIO, LUCIA MESAROSOVA, JASPER J. ANINK, SILVIA KOCHEN, PATRICIA SOLÍS, SILVIA ODDO, HECTOR KONOPKA, ANAND M. IYER, ANGELIKA MÜHLEBNER, PAUL J. LUCASSEN, ELEONORA ARONICA, ERWIN A. VAN VLIET.

EPILEPSIA

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2020

0013-9580

Objective: Depressive disorders are common among about 50% of the patients with drug-resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamic-pituitary-adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we here set out to investigate expression of the GR in the hippocampus, an important brain region for HPA axis feedback, from patients with drug-resistant TLE, with and without comorbid depression.Methods: GR expression was studied using immunohistochemistry on hippocampal sections from well-characterized TLE patients with depression (TLE+D, n=14) and without depression (TLE-D, n=12) who underwent surgery for drug-resistant epilepsy, as well as on hippocampal sections from autopsy control cases (n=9). Video-EEG, MRI, psychiatric and memory assessments were performed prior to surgery. Results: Abundant GR-immunoreactivity was present in dentate gyrus granule cells and CA1 pyramidal cells of controls. In contrast, neuronal GR expression was lower in patients with TLE, particularly in the TLE+D group. Quantitative analysis showed a smaller GR+ area in TLE+D as compared to TLE-D patients and controls. Furthermore, the ratio between the number of GR+/NeuN+ cells was lower in patients with TLE+D as compared to TLE-D and negatively correlated with the depression severity based on psychiatric history. The expression of the GR was also lower in glial cells of TLE+D compared to TLE-D patients and negatively correlated to the severity of depression.Significance: Reduced hippocampal GR expression may be involved in the etiology of depression in patients with TLE and could constitute a biological marker of depression in these patients.