id_917. EFFECT OF SSR504734, A SELECTIVE GLYCINE TRANSPORTER TYPE 1 INHIBITOR, ON EPILEPTOGENESIS AND DNA METHYLATION STATUS IN THE AMYGDALA KINDLING MODEL IN MICE
Agata Matuła1,2, Nikola Gapińska1,2, Piotr Wlaź1, Anna Rafało-Ulińska4, Bernadeta Szewczyk4, Krzysztof Kamiński4, Marcin Jakubiec4, Michał Abram4, Katarzyna Ciepiela5, Weronika Woźniak1,2, Katarzyna Socała1
1 Biomedical Research Laboratory, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
2 Doctoral School of Quantitative and Natural Sciences, Maria Curie-Skłodowska University, Weteranów 18, 20-038 Lublin, Poland
3 Department of Neurobiology, Jerzy Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland
4 Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
5 Selvita S.A., Bobrzyńskiego 14, 30-348 Kraków, Poland
INTRODUCTION: Glycine is a unique neurotransmitter in the central nervous system that modulates both glycinergic and glutamatergic transmission. Through glycine reuptake and regulation of its concentration in the synaptic cleft, the glycine transporter type 1 (GlyT1) may influence seizure activity and modulate hippocampal network function; however, knowledge in this area remains limited.
AIM(S): The aim of the study was to investigate the effect of SSR504734, a GlyT1 inhibitor, on the process of epileptogenesis and DNA methylation status in the amygdala kindling model in mice.
METHOD(S): CD-1 mice were divided into four groups: kindled and sham (non-kindled), receiving either SSR504734 at a dose of 30 mg/kg or saline throughout the kindling procedure. After completion of the kindling protocol, animals were sacrificed by decapitation, and the hippocampus and brainstem were collected for further analyses. Levels of DNA 5-mC and 5-hmC were determined using a colorimetric method.
RESULTS: SSR504734 did not inhibit the process of epileptogenesis in the amygdala kindling model. Changes in the levels of 5-mC and 5-hmC were observed in the hippocampus and brainstem in animals subjected to kindling and after administration of SSR504734, however, the differences were not statistically significant.
CONCLUSIONS: The presented results indicate that SSR504734 does not inhibit the process of epileptogenesis. However, the compound induced epigenetic changes in the brain by decreasing DNA methylation levels and increasing demethylation, which may suggest a potential influence on the process of epileptogenesis, although such functional effects were not observed.
FINANCIAL SUPPORT: Research project was funded by the National Science Centre, Poland (grant no. UMO-2021/41/NZ7/00328).