Early developmental alterations in GABAergic protein expression in fragile X knockout mice
Open accessAbstract
Fragile X syndrome is the most common heritable form of mental retardation. It is caused by silencing of the Fmr1 gene and the absence of the encoded protein. The purpose of this study was to examine global protein expression levels of GABA(A) and GABA(B) receptors, and GABAergic enzymes and trafficking proteins in fragile X knockout mice during brain maturation. Quantitative western blotting of homogenates of forebrain revealed that the levels of GABA(A) beta1 and beta3, GABA(B)-R1, NKCC1, KCC2, gephyrin and ubiquilin were not significantly different from wild-type mice at any of the postnatal time points examined. In contrast, the GABA(A) receptor alpha1, beta2, and delta subunits, and the GABA enzymes GABA transaminase and succinic semialdehyde dehydrogenase were down-regulated during postnatal development, while GAD65 was up-regulated in the adult knockout mouse brain. The GABA(A) receptor alpha1 and beta2 subunits displayed a divergent pattern of developmental expression whereby alpha1 was reduced in the immature brain but regained a level of expression similar to wild-type mice by adulthood, while the expression of beta2 was similar to wild-types at postnatal day 5 but reduced at day 12 and in the adult brain. The GABA(A) receptor delta subunit and the GABA catabolic enzymes GABA transaminase and succinic semialdehyde dehydrogenase were simultaneously but transiently decreased only at postnatal day 12. Our results demonstrate that GABA(A) receptor subunits and GABA enzymes display complex patterns of changes during brain development suggesting that dynamic interactions may occur between GABA transmitter levels and GABA receptors in fragile X syndrome.
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GABA A receptor subunit α1 is down-regulated during postnatal cortical development in Fmr1 knock-out mice.
“Moreover, there is a down-regulation of GABA A receptor subunit α1 during postnatal cortical development in Fmr1 KO mice (Adusei et al. 2010), a subunit normally enriched at PV cell/pyramidal cell synapses.”
From Genetic Reduction of Matrix Metalloproteinase-9 Promotes Formation of Perineuronal Nets Around Parvalbumin-Expressing Interneurons and Normalizes Auditory Cortex Responses in Developing Fmr1 Knock-Out Mice (2018) · cites this paper as Adusei et al. 2010
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Self-citation
- Authors
- Adusei, D. C., Pacey, L. K. K., Chen, D., & Hampson, D. R.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Hampson, David R.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 59
- Issue
- 3
- Pages
- 167-171
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W1976450222
- Cited by
- 139
- References
- 175
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 10 · 2017: 9 · 2016: 12 · 2015: 16 · 2014: 16 · 2013: 10 · 2012: 11
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Library and Archives Canada (Government of Canada) (submittedVersion)
- TSpace (University of Toronto) (submittedVersion)
- Funders
- National Institutes of Health (U24NS050606)
- University of California, Davis
- Canadian Institutes of Health Research
- 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, Fmr1 knockout mice, GABAergic system, GABAA receptor subunits, GABAB receptors, GABA transaminase, succinic semialdehyde dehydrogenase, GAD65, brain maturation, postnatal development, GABA catabolism, gephyrin, NKCC1, KCC2, ubiquilin
- MeSH terms
- Autophagy-Related Proteins, K Cl- Cotransporters, Age Factors, 4-Aminobutyrate Transaminase, Animals, Animals, Newborn, Carrier Proteins, gamma-Aminobutyric Acid, Membrane Proteins, Mice, Inbred C57BL, Receptors, GABA-A, Receptors, GABA-B, Mice, Knockout, Gene Expression Regulation, Developmental, Symporters, Sodium-Potassium-Chloride Symporters, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Mice, Fragile X Messenger Ribonucleoprotein 1, Solute Carrier Family 12, Member 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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