Cited by 139Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchDown syndrome and intellectual disability research

Early developmental alterations in GABAergic protein expression in fragile X knockout mice

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Adusei, Daniel C., Pacey, Laura K.K., Chen, Duke, Hampson, David R.·2010·Neuropharmacology

Abstract

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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Crossref · 10.1016/j.neuropharm.2010.05.002

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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
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

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