Mesial temporal lobe epilepsy with psychiatric comorbidities: a place for differential neuroinflammatory interplay

Author(s)

Kandratavicius, Ludmyla ^{[1, 2]} ; Peixoto-Santos, Jose Eduardo ^[1] ; Monteiro, Mariana Raquel ^[1] ; Scandiuzzi, Renata Caldo ^[1] ; Carlotti, Jr., Carlos Gilberto ^[3] ; Assirati, Jr., Joao Alberto ^[3] ; Hallak, Jaime Eduardo ^{[1, 2, 4]} ; Leite, Joao Pereira ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPN, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Ribeirao Preto - Brazil

^[4] INCT TM CNPq, Natl Inst Sci & Technol Translat Med, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: JOURNAL OF NEUROINFLAMMATION; v. 12, FEB 25 2015.
• Web of Science Citations: 15

Abstract

Background: Despite the strong association between epilepsy and psychiatric comorbidities, few biological substrates are currently described. We have previously reported neuropathological alterations in mesial temporal lobe epilepsy (MTLE) patients with major depression and psychosis that suggest a morphological and neurochemical basis for psychopathological symptoms. Neuroinflammatory-related structures and molecules might be part of the altered neurochemical milieu underlying the association between epilepsy and psychiatric comorbidities, and such features have not been previously investigated in humans. Methods: MTLE hippocampi of subjects without psychiatric history (MTLEW), MTLE + major depression (MTLE + D), and MTLE + interictal psychosis (MTLE + P) derived from epilepsy surgery and control necropsies were investigated for reactive astrocytes (glial fibrillary acidic protein (GFAP)), activated microglia (human leukocyte antigen, MHC class II (HLA-DR)), glial metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) immunohistochemistry. Results: We found an increased GFAP immunoreactive area in the molecular layers, granule cell layer, and cornus ammonis region 2 (CA2) and cornus ammonis region 1 (CA1) of MTLEW and MTLE + P, respectively, compared to MTLE + D. HLA-DR immunoreactive area was higher in cornus ammonis region 3 (CA3) of MTLE + P, compared to MTLE + D and MTLEW, and in the hilus, when compared to MTLEW. MTLEW cases showed increased MT-I/II area in the granule cell layer and CA1, compared to MTLE + P, and in the parasubiculum, when compared to MTLE + D and MTLE + P. Differences between MTLE and control, such as astrogliosis, microgliosis, increased MT-I/II, and decreased perivascular AQP4 in the epileptogenic hippocampus, were in agreement to what is currently described in the literature. Conclusions: Neuroinflammatory-related molecules in MTLE hippocampus show a distinct pattern of expression when patients present with a comorbid psychiatric diagnosis, similar to what is found in the pure forms of schizophrenia and major depression. Future studies focusing on inflammatory characteristics of MTLE with psychiatric comorbidities might help in the design of better therapeutic strategies. (AU)

• FAPESP's process: 11/23691-3 - Neuropathological characterization of amygdala and temporal cortex of temporal lobe epilepsy patients with or without psychiatric comorbidities
• Grantee: Mariana Raquel Monteiro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 05/56447-7 - Research through images from high field magnetic resonance aimed at studies in humans
• Grantee: João Pereira Leite
• Support Opportunities: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants