Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome

Autor(es)

Victorino, Daniella B. ^{[1, 2]} ; Pinheiro, Daniel J. L. L. ^[1] ; Scott-McKean, Jonah J. ^[2] ; Barker, Sarah ^[2] ; Stasko, Melissa R. ^[2] ; Faber, Jean ^[1] ; Scorza, Carla A. ^[1] ; Costa, Alberto C. S. ^{[3, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Paulista Med Sch, Dept Neurol & Neurosurg, Discipline Neurosci, Sao Paulo, SP - Brazil

^[2] Case Western Reserve Univ, Dept Pediat, Div Pediat Neurol, 11100 Euclid Ave, Mail Stop RBC 6090, Cleveland, OH 44106 - USA

^[3] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 - USA

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 MAY 4 2021.
• Citações Web of Science: 0

Resumo

Mounting evidence implicates dysfunctional GABA(A)R-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABA(A)R positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS. (AU)

• Processo FAPESP: 16/17746-3 - Avaliação dos efeitos de benzodiazepínicos sobre a atividade eletrofisiológica cerebral in vivo e a viabilidade neuronal in vitro em camundongos da linhagem Ts65Dn
• Beneficiário: Daniella Balduino Victorino
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/10131-9 - Efeitos da modulação alostérica positiva sobre as propriedades eletrofisiológicas da sinalização mediada por receptores GABAA em camundongos Ts65Dn e neurônios derivados de células-tronco pluripotentes induzidas de pessoas com a síndrome de Down
• Beneficiário: Daniella Balduino Victorino
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado