The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Decreased expression of the GABAA receptor in fragile X syndrome
Abstract
After our initial discovery of under expression of the GABA(A) receptor delta subunit in a genome wide screening for differentially expressed mRNAs in brain of fragile X mice, a validated model for fragile X mental retardation syndrome, we analyzed expression of the 17 remaining subunits of the GABA(A) receptor using real-time PCR. We confirmed nearly 50% under expression of the delta subunit and found a significant 35%-50% reduction in expression of 7 additional subunit mRNAs, namely alpha(1), alpha(3), and alpha(4), beta(1) and beta(2) and gamma(1) and gamma(2), in fragile X mice compared to wild-type littermates. In concordance with previous results, under expression was found in cortex, but not in cerebellum. Moreover, decreased expression of specific GABA(A) receptor subunits in fragile X syndrome seems to be an evolutionary conserved hallmark since in the fragile X fly (Drosophila melanogaster) model we also found almost 50% under expression of all 3 subunits which make up the invertebrate GABA receptor, namely Grd, Rdl and Lcch3. In addition, we demonstrated a direct correlation between the amount of dFmrp and the expression of the GABA receptor subunits Rdl and Grd. Our results add evidence to previous observations of an altered GABAergic system in fragile X syndrome. Because GABA(A) receptors are the major inhibitory receptors in brain, involved in anxiety, depression, insomnia, learning and memory and epilepsy, processes also disturbed in fragile X patients, the well described GABA(A) receptor pharmacology might open new powerful opportunities for treatment of the behavioral and epileptic phenotype associated with fragile X syndrome.
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“The GABA receptor system has also been reported as downregulated in FXS, partially due to destabilization of the mRNAs encoding the GABA receptor subunits (76,80,113).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [113]
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Absence of expression of the FMR-1 gene in fragile X syndrome
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Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,108
Abnormal dendritic spines in fragile X knockout mice: Maturation and pruning deficits
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Encyclopedia of molecular cell biology and molecular medicine
Meyers, R. A. (2004) · Cited by 613
Evidence that fragile X mental retardation protein is a negative regulator of translation
Laggerbauer, B. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.4.329 · Cited by 571
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Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and Function
Bassell, G. J., & Warren, S. T. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.004 · Cited by 1,051
Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838
Self-citationMolecular Mechanisms of Fragile X Syndrome: A Twenty-Year Perspective
Santoro, M. R., Bray, S. M., & Warren, S. T. (2012) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011811-132457 · Cited by 528
Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516
Dictenberg, J. B., Swanger, S. A., Antar, L. N., Singer, R. H., & Bassell, G. J. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.04.003 · Cited by 511
Metadata
- Authors
- D'Hulst, C., De Geest, N., Reeve, S. P., Van Dam, D., De Deyn, P. P., Hassan, B. A., & Kooy, R. F.
- Affiliations
- KU Leuven (BE)
- University of Antwerp (BE)
- Corresponding author
- Kooy, R. Frank
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 1121
- Issue
- 1
- Pages
- 238-245
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1972740284
- Cited by
- 318
- References
- 47
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 5 · 2023: 14 · 2022: 20 · 2021: 10 · 2020: 18 · 2019: 15 · 2018: 10 · 2017: 18 · 2016: 16 · 2015: 28 · 2014: 26 · 2013: 22 · 2012: 24
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- 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, GABAA receptor, GABA receptor subunits, Drosophila, FMRP, GABAergic system, gene expression, cortex, cerebellum, epilepsy, anxiety, learning and memory
- MeSH terms
- Animals, Crosses, Genetic, Disease Models, Animal, Fragile X Syndrome, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation, Receptors, GABA-A, RNA, Messenger, Down-Regulation, Mice, Fragile X Messenger Ribonucleoprotein 1
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