| First Author | Buzzi A | Year | 2006 |
| Journal | Brain Res | Volume | 1090 |
| Issue | 1 | Pages | 15-22 |
| PubMed ID | 16647690 | Mgi Jnum | J:109671 |
| Mgi Id | MGI:3629451 | Doi | 10.1016/j.brainres.2006.02.131 |
| Citation | Buzzi A, et al. (2006) Succinic Semialdehyde Dehydrogenase Deficiency: GABA(B) receptor-mediated function. Brain Res 1090(1):15-22 |
| abstractText | 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 GABA(B)R receptor (GABA(B)R). We tested the hypothesis that both GHBR and GABA(B)R-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 GABA(B)R in mutant mice made deficient in SSADH (SSADH(-/-)). There was a significant decrease in binding of the specific GABA(B)R antagonist, [(3)H]CGP-54626A at postnatal day (PN)7 and PN14 in SSADH(-/-) when compared to wild type control animals (SSADH(+/+)), particularly in hippocampus. GABA(B)R-mediated synaptic potentials were decreased in SSADH(-/-). Immunoblot analysis of GABA(B)R1a, R1b, and R2 in SSADH(-/-) indicated a trend towards a region-specific and time-dependent decrease of GABA(B)R subunit protein expression. There was no difference between SSADH(-/-) and wild type in binding of either [(3)H]GHB or a specific GHBR antagonist to the GHBR. These data suggest that the elevated levels of GABA and GHB that occur in SSADH(-/-) lead to a use-dependent decrease in GABA(B)R-mediated function and raise the possibility that this GHB- and GABA-induced perturbation of GABA(B)R could play a role in the pathogenesis of the seizures and mental retardation observed in SSADH deficiency. |
