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

D?ALESSIO, LUCIANA; MESAROSOVA, LUCIA; ANINK, JASPER J.; KOCHEN, SILVIA; SOLÍS, PATRICIA; ODDO, SILVIA; KONOPKA, HECTOR; IYER, ANAND M.; VLIET, ERWIN A.

EPILEPSIA

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020 p. 1 - 11

0013-9580

Objective: Depressive disorders are common among about 50% of the patientswith drug-resistant temporal lobe epilepsy (TLE). The underlying etiology remainselusive, but hypothalamus-pituitary-adrenal (HPA) axis activation due to changesin glucocorticoid receptor (GR) protein expression could play an important role.Therefore, we set out to investigate expression of the GR in the hippocampus, animportant brain region for HPA axis feedback, of patients with drug-resistant TLE,with and without comorbid depression.Methods: GR expression was studied using immunohistochemistry on hippocampalsections from well-characterized TLE patients with depression (TLE + D, n = 14)and without depression (TLE − D, n = 12) who underwent surgery for drug-resistantepilepsy, as well as on hippocampal sections from autopsy control cases (n = 9).Video?electroencephalography (EEG), magnetic resonance imaging (MRI), andpsychiatric and memory assessments were performed prior to surgery.Results: Abundant GR immunoreactivity was present in dentate gyrus granulecells and CA1 pyramidal cells of controls. In contrast, neuronal GR expression waslower in patients with TLE, particularly in the TLE + D group. Quantitative analysisshowed a smaller GR+ area in TLE + D as compared to TLE − D patients andcontrols. Furthermore, the ratio between the number of GR+/NeuN+ cells was lowerin patients with TLE + D as compared to TLE − D and correlated negatively withthe depression severity based on psychiatric history. The expression of the GR wasalso lower in glial cells of TLE + D compared to TLE − D patients and correlatednegatively to the severity of depression.