Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function

Brain Research
Andrea BuzziO C Snead

Abstract

The succinic semialdehyde dehydrogenase (SSADH) null mouse (SSADH(-/-)) represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. In physiological concentrations, GHB acts at the GHB receptor (GHBR), but in high concentrations such as those observed in the brains of children with SSADH deficiency, GHB is thought to be a direct agonist at the GABABR receptor (GABABR). We tested the hypothesis that both GHBR and GABABR-mediated function are perturbed in SSADH deficiency. Therefore, we examined the high affinity binding site for GHB as well as the expression and function of the GABABR in mutant mice made deficient in SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific GABABR antagonist, [3H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-) when compared to wild type control animals (SSADH(+/+)), particularly in hippocampus. GABABR-mediated synaptic potentials were decreased in SSADH(-/-). Immunoblot analysis of GABABR1a, R1b, and R2 in SSADH(-/-) indicated a trend towards a region-specific and time-dependent decrease of GABABR subunit protein ex...Continue Reading

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Citations

Jan 28, 2009·Journal of Inherited Metabolic Disease·P L PearlW H Theodore
Jan 7, 2010·Journal of Inherited Metabolic Disease·Megumi TsujiHitoshi Osaka
Mar 14, 2013·Annual Review of Economics·Daniel J BenjaminPaul Lichtenstein
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May 24, 2017·International Journal of Legal Medicine·Lena-Maria MehlingCornelius Courts
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Jan 5, 2021·Journal of Child Neurology·Phillip L PearlK Michael Gibson
Jan 26, 2021·Clinical Case Reports·Malak Ali AlghamdiStefan T Arold

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