title: Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome.
abstract: 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 system in 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.
authors.affiliation: Universidade Federal de São Paulo - Unifesp/EPM, Department of Neurology and Neurosurgery - Laboratório de Neurociências, São Paulo, SP, Brazil. Electronic address: bhsa83@gmail.com.
authors.forename: Bruno Henrique Silva
authors.initials: BH
authors.lastname: Araujo
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; Centro Sul Brasileiro de Pesquisa, Extensão e Pós-Graduação, CENSUPEG, Joinville, SC, Brazil.
authors.forename: Laila Brito
authors.initials: LB
authors.lastname: Torres
authors.affiliation: Universidade Federal de São Paulo - Unifesp/EPM, Department of Neurology and Neurosurgery, São Paulo, SP, Brazil.
authors.forename: Laura Maria F F
authors.initials: LM
authors.lastname: Guilhoto
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D004314:Down Syndrome / Q000453:epidemiology / Q000503:physiopathology*; D004827:Epilepsy / Q000453:epidemiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D051379:Mice; D009433:Neural Inhibition / Q000235:genetics*; D018377:Neurotransmitter Agents / Q000502:physiology; D015995:Prevalence; D011963:Receptors, GABA-A / Q000502:physiology; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid
keywords: Down syndrome; Epilepsy; GABA; Infantile spasms; LOMEDS