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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 8
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 11, n. 1 MAY 4 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 16/17746-3 - Evaluation of the effects of benzodiazepines on the in vivo electrophysiological activity of the brain and in vitro neuronal viability in the Ts65Dn mouse model
Grantee:Daniella Balduino Victorino
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/10131-9 - Effects of positive allosteric modulation on electrophysiological properties of GABAAR signaling in Ts65Dn mice and induced pluripotent stem cell-derived neurons from persons with Down syndrome
Grantee:Daniella Balduino Victorino
Support type: Scholarships abroad - Research Internship - Doctorate