RESUMO
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.
Assuntos
Transtorno Depressivo/metabolismo , Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Receptores de Glucocorticoides/metabolismo , Adulto , Idoso , Região CA1 Hipocampal/metabolismo , Estudos de Casos e Controles , Giro Denteado/metabolismo , Transtorno Depressivo/complicações , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/cirurgia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Sistema Hipófise-Suprarrenal , Células Piramidais/metabolismo , Adulto JovemRESUMO
Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional states.
Assuntos
Hanseníase/imunologia , Hanseníase/patologia , Humanos , Hanseníase/sangueRESUMO
Advances concerning the hosts' immune response to Mycobacterium leprae infection have focused on elucidating the immune pathomechanisms involved, with the hope that predictive diagnostic and prognostic parameters (biomarkers) for field use would emerge; however, improvements in our understanding of the immunologic responses to this complex disease have, to date, somewhat failed to provide the effective and robust methods for improving its predictive diagnosis in the field situation, particularly in those patients suffering from paucibacillary disease. In this contribution we have attempted to review some of the advances both in the immunology and immunopathology of leprosy, and also highlight the limited clusters of immune parameters that are now available. Most importantly, we point out the limitations that still prevail in the provision of effective biomarkers in the field situation for either: (1) the diagnosis of indeterminate disease, (2) predictive diagnosis of individuals developing reactional states, (3) monitoring efficacy of treatment, or (4) monitoring treatment of reactional states.