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Cited by 141Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome

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Contestabile, Andrea, Magara, Salvatore, Cancedda, Laura·2017·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2017.00054PMC PMC5339239
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Abstract

Down syndrome (DS) is a genetic disorder caused by the presence of a third copy of chromosome 21. DS affects multiple organs, but it invariably results in altered brain development and diverse degrees of intellectual disability. A large body of evidence has shown that synaptic deficits and memory impairment are largely determined by altered GABAergic signaling in trisomic mouse models of DS. These alterations arise during brain development while extending into adulthood, and include genesis of GABAergic neurons, variation of the inhibitory drive and modifications in the control of neural-network excitability. Accordingly, different pharmacological interventions targeting GABAergic signaling have proven promising preclinical approaches to rescue cognitive impairment in DS mouse models. In this review, we will discuss recent data regarding the complex scenario of GABAergic dysfunctions in the trisomic brain of DS mice and patients, and we will evaluate the state of current clinical research targeting GABAergic signaling in individuals with DS.

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Authors
Contestabile, A., Magara, S., & Cancedda, L.
Affiliations
Italian Institute of Technology (IT)
Corresponding author
  • Contestabile, Andrea
  • Cancedda, Laura
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2017-03-07
Volume
11
Pages
54-54
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2017.00054
PMC
PMC5339239
OpenAlex
W2592667503
Cited by
141
References
294
Citations by year
2026: 10 · 2025: 10 · 2024: 10 · 2023: 13 · 2022: 17 · 2021: 37 · 2020: 7 · 2019: 16 · 2018: 15 · 2017: 5 · 2016: 1
FWCI
1.91
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Fondazione Telethon (GGP15043, GGP13187, TCP15021)
  • Fondation Jérôme Lejeune (254-CA2014A, 1266_CL2014A)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Down syndrome, GABAergic neurotransmission, intellectual disability, inhibitory interneurons, synaptic deficits, memory impairment, pharmacological interventions, cognitive impairment

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