Frank Kooy, University of Antwerp, Belgique: "GABAergic abnormalities in the fragile X syndrome to the rescue"
Seminaire DNF et CIG
Tuesday 28 January 2020 (12h15 - 13h15) - Bugnon 9 - Grand Auditoire
Invité par Claudia Bagni, email@example.com et Alexandre Reymond, firstname.lastname@example.org
Many pathways have been involved in pathophysiology of the fragile X syndrome, one of the more frequent genetic causes of intellectual disability and autism. This review highlights the recent insights in the role the abnormalities in the GABAergic system play in the disorder. Since the initial observations made that the expression of specific subunits of the GABA(A) receptor were underexpressed in the fragile X knockout mouse model more than a decade ago, evidence has accumulated that the expression of approximately half of the GABAergic system is compromised in multiple species, including in fragile X patients. Functional consequences of the GABAergic deficiencies could be measured using whole-cell voltage clamp recordings. In an in vitro model of cortical microcircuitry we observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single - cell phenotypes Pharmalogical treatment with agonist of the receptor was been able to restore several behavioral deficits in the fragile X mouse model, including seizures, marble burying and, in part, prepulse inhibition. Trials in patients with the same agonist have demonstrated encouraging post-hoc results in the most severely affected patients, although no effect could be demonstrated in the patient group as a whole.. In conclusion, there can be little doubt that the GABAergic system is compromised in the fragile X syndrome, but also in other neurodevelopmental disorders, and that these abnormalities contribute to the clinical abnormalities observed.
DNF et CIG