Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2022) 84 PS1-04-30 | DOI: 10.1530/endoabs.84.PS1-04-30

ETA2022 Poster Presentations Thyroid Hormone Transporters and Development (8 abstracts)

Impact of thyroid hormone transport on the hippocampal gabaergic and glutamatergic system

Andrea Alcaide Martin 1 , Heike Heuer 1 & Steffen Mayerl 2


1University Hospital Essen, Dept. of Endocrinology, Diabetes and Metabolism, Essen, Germany; 2University Hospital Essen, Dept. of Endocrinology, Diabetes & Metabolism, Essen, Germany


Patients with inactivating mutations in MCT8, known as Allan-Herndon-Dudley syndrome (AHDS), present a severe form of psychomotor retardation and, frequently, epileptic seizures of unknown etiology. These neurological symptoms are thought to arise due to an impaired transport of thyroid hormones (TH) across the blood brain barrier and/or into the neural cells. As a consequence of species-specific differences in the expression of the T4-specific organic anion transporter polypeptide 1c1 (Oatp1c1), the AHDS pathology is only replicated in Mct8/Oatp1c1 double knockout (M/O-dKO) mice. Here, we address the question whether alterations in the hippocampus, a brain area central in epilepsy disorder, underpin the seizure susceptibility of MCT8 patients. To this end, we first characterize the inhibitory GABAergic system and the excitatory glutamatergic system in the hippocampus at different postnatal stages using the M/O-dKO mouse model. At P12, immunofluorescence studies showed a severe decrease in Gad67 levels, a general GABAergic marker, in M/O-dKO mice. Likewise, numbers of GABAergic neurons positive for parvalbumin were strongly reduced, while there was a significant increase in somatostatin positive interneurons in M/O-dKO mice. These cellular changes are transient as at P120, no differences were visible in M/O-dKO mice any longer. In contrast, qPCR analysis of hippocampal homogenates at P12 and P120 revealed an increased expression of GABA transporters and GABA transaminase in adult M/O-dKO animals, indicating increased GABA reuptake and metabolism, respectively. On the other hand, the expression levels of kainite receptor subunits such as GluR6 or KA1 were increased in adult M/O-dKO mice, suggesting an abnormal glutamate signaling in the hippocampus. Together, these results point to an altered development of both the inhibitory and the excitatory system that can potentially impact seizure susceptibility in the absence of Mct8 and Oatp1c1.

Volume 84

44th Annual Meeting of the European Thyroid Association (ETA) 2022

Brussels, Belgium
10 Sep 2022 - 13 Sep 2022

European Thyroid Association 

Browse other volumes

Article tools

My recent searches

No recent searches.