Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome

Autor(es)

Silva Araujo, Bruno Henrique ^[1] ; Torres, Laila Brito ^{[2, 3]} ; Guilhoto, Laura Maria F. F. ^[4]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Unifesp EPM, Dept Neurol & Neurosurg, Lab Neurociencias, Sao Paulo, SP - Brazil

^[2] Hosp Israelita Albert Einstein, Sao Paulo, SP - Brazil

^[3] Ctr Sul Brasileiro Pesquisa Extensao & Posgrad, CENSUPEG, Joinville, SC - Brazil

^[4] Univ Fed Sao Paulo, Unifesp EPM, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Epilepsy & Behavior; v. 53, p. 120-125, DEC 2015.
• Citações Web of Science: 4

Resumo

Down syndrome(DS) is the most common cause of genetic intellectual disability, and the trisomy 21 is associated with more than 80 clinical traits, including higher risk for epilepsy. Several hypotheses have been put forward to explain the mechanisms underlying increased seizure susceptibility in DS: inherent structural brain abnormalities, abnormal cortical lamination, disruption of normal dendritic morphology, and underdeveloped synaptic profiles. A deficiency or loss of GABA inhibition is hypothesized to be one of the main alterations related to the epileptogenic process. Paradoxically, enhanced GABA inhibition has also been reported to promote seizures. One major functional abnormality observed in the brains of individuals and mouse models with DS appears to be an imbalance between excitatory and inhibitory neurotransmission, with excessive inhibitory brain function. This review discusses the GABAergic systemin the human DS brain and the possible implication of the GABAergic network circuit in the epileptogenic process in individuals where the pathogenetic basis for epilepsy is unknown. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 14/08049-1 - Papel dos astrócitos na plasticidade sináptica de neurônios derivados de células tronco pluripotente induzidas de pacientes com Síndrome de Down
• Beneficiário: Bruno Henrique Silva Araujo Torres
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado