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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROINFLAMMATION; v. 12, FEB 25 2015.
• Citações Web of Science: 15

Resumo

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)

• Processo FAPESP: 11/23691-3 - Caracterização neuropatológica da amígdala e córtex temporal de pacientes com epilepsia do lobo temporal associada ou não a comorbidades psiquiátricas
• Beneficiário: Mariana Raquel Monteiro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 05/56447-7 - Pesquisa através de imagens por ressonância magnética de alto campo destinadas a estudos em humanos
• Beneficiário: João Pereira Leite
• Modalidade de apoio: Auxílio à Pesquisa - Programa CINAPCE - Temático
• Processo FAPESP: 10/51515-2 - Estudo das relacoes entre populacoes celulares, expressao de aquaporina-4 e sulfato de condroitina com o tempo de relaxamento e taxa de transferencia de magnetizacao no hipocampo de pacientes com...
• Beneficiário: José Eduardo Peixoto Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado