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Cited by 30Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchDown syndrome and intellectual disability research

Impaired GABA neural circuits are critical for fragile X syndrome.

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Gao, Fei, Qi, Lijun, Yang, Zhongzhen, Yang, Tao, Zhang, Yan, Xu, Hui, Zhao, Huan·2018·Neural Plasticity
DOI 10.1155/2018/8423420PMC PMC6192167
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Abstract

Fragile X syndrome (FXS) is an inheritable neuropsychological disease caused by silence of the fmr1 gene and the deficiency of Fragile X mental retardation protein (FMRP). Patients present neuronal alterations that lead to severe intellectual disability and altered sleep rhythms. However, the neural circuit mechanisms underlying FXS remain unclear. Previous studies have suggested that metabolic glutamate and gamma-aminobutyric acid (GABA) receptors/circuits are two counter-balanced factors involved in FXS pathophysiology. More and more studies demonstrated that attenuated GABAergic circuits in the absence of FMRP are critical for abnormal progression of FXS. Here, we reviewed the changes of GABA neural circuits that were attributed to intellectual-deficient FXS, from several aspects including deregulated GABA metabolism, decreased expressions of GABA receptor subunits, and impaired GABAergic neural circuits. Furthermore, the activities of GABA neural circuits are modulated by circadian rhythm of FMRP metabolism and reviewed the abnormal condition of FXS mice or patients.

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  • Reduction of several GABA receptor subunits in various brain regions associates with reduced expression of GABA metabolizing enzymes and reduced numbers of parvalbumin positive neurons in the Fmr1 KO mouse.

    “Reduction of several GABA receptor subunits in various brain regions associates with reduced expression of GABA metabolizing enzymes and reduced numbers of parvalbumin (PV) positive neurons in the Fmr1 KO mouse (Gao et al., 2018; Van der Aa and Kooy, 2020).”

    From Astrocytes in fragile X syndrome (2024) · cites this paper as Gao et al., 2018

    Section 3 (page unavailable) reports reduced tonic GABAA receptor subunits associated with reduced tonic currents in an Fmr1 knockout mouse, but does not establish reductions of several subunits across various brain regions. Section 2 (page unavailable) discusses GABA metabolism without reporting reduced expression of its enzymes, and the searched passages do not report fewer parvalbumin-positive neurons. (LLM, conf=0.86)

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Cited by

Sorted by citations

  • Astrocytes in fragile X syndrome

    Talvio, K., & Castrén, M. L. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1322541 · Cited by 8 · see citing works

    “…are dysregulated in the absence of FMRP. Reduction of several GABA receptor subunits in various brain regions associates with reduced expression of GABA metabolizing enzymes and reduced numbers of parvalbumin (PV) positive neurons in the Fmr1 KO mouse (Gao et al., 2018; Van der Aa and Kooy, 2020).”
    Background

Authors
Gao, F., Qi, L., Yang, Z., Yang, T., Zhang, Y., Xu, H., & Zhao, H.
Affiliations
  • Heze Municipal Hospital (CN)
  • Tang Du Hospital (CN)
  • Air Force Medical University (CN)
Corresponding author
  • Xu, Hui
  • Zhao, Huan
ORCID
Venue
Neural Plasticity
Publisher
Wiley
Published
2018-10-03
Volume
2018
Pages
1-7
ISSN
  • 1687-5443 (ISSN-L)
  • 2090-5904
DOI
10.1155/2018/8423420
PMC
PMC6192167
OpenAlex
W2894829624
Cited by
30
References
8
Citations by year
2026: 2 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 2
FWCI
0.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Neural Plasticity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81671081, 31371120)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords
fragile X syndrome, FMRP, GABAergic circuits, GABA metabolism, GABA receptor subunits, intellectual disability, sleep disorders, circadian rhythm
MeSH terms
Animals, Brain, Fragile X Syndrome, gamma-Aminobutyric Acid, Humans, Nerve Net, Receptors, GABA, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1, GABAergic Neurons

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