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Reduced expression of the glucocorticoid receptor in the hippocampus of patients with drug‐resistant temporal lobe epilepsy and comorbid depression
Author(s) -
D’Alessio Luciana,
Mesarosova Lucia,
Anink Jasper J.,
Kochen Silvia,
Solís Patricia,
Oddo Silvia,
Konopka Hector,
Iyer Anand M.,
Mühlebner Angelika,
Lucassen Paul J.,
Aronica Eleonora,
Vliet Erwin A.
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16598
Subject(s) - temporal lobe , dentate gyrus , epilepsy , hippocampus , hippocampal formation , glucocorticoid receptor , medicine , psychology , glucocorticoid , endocrinology , neuroscience
Abstract Objective Depressive disorders are common among about 50% of the patients with drug‐resistant temporal lobe epilepsy (TLE). The underlying etiology remains elusive, but hypothalamus‐pituitary‐adrenal (HPA) axis activation due to changes in glucocorticoid receptor (GR) protein expression could play an important role. Therefore, we set out to investigate expression of the GR in the hippocampus, an important 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 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–electroencephalography (EEG), magnetic resonance imaging (MRI), and 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 correlated negatively 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 correlated negatively 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.