Characterisation of circadian dynamics of the transcription factor Zbtb14 in naïve and epileptic mice : PhD thesis

Güntan, Ilke

Characterisation of circadian dynamics of the transcription factor Zbtb14 in naïve and epileptic mice : PhD thesis

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Title: Characterisation of circadian dynamics of the transcription factor Zbtb14 in naïve and epileptic mice : PhD thesis

Abstract:

While the relationship between epilepsy and circadian dysregulation is known, we know very little about circadian oscillations of the transcription factors which are responsible from modulating the gene expression in health and disease pathologies. This study aims to characterise circadian dynamics of one of the identified and prominent transcription factors in epilepsy – the Zbtb14. In pursuit of this objective, protein rhythmicity of the Zbtb14 is observed in the ventral and dorsal hippocampus and the somatosensory cortex using immunochemistry, and in cytoplasmic and nuclear protein extracts of the hippocampus using western blot. The downregulated genes with ZF5 motif in their promoters identified in an in vitro model of epileptiform discharges is characterised. Zbtb14 protein expression is investigated in two time points in an in vivo model of epilepsy model. The study showed that Zbtb14 protein only has a rhythmic expression in the ventral hippocampus but not in the dorsal hippocampus and the somatosensory cortex. Additionally, the cytoplasmic and nuclear dynamics of the Zbtb14 protein are different. I identified the downregulated genes in in vitro model of epileptiform discharges are mainly responsible from synaptic plasticity and transmission. Furthermore, the epilepsy pathology affected the Zbtb14 transcription factor expression in a time-dependent manner. My research shows that the studies on circadian regulations of the transcription factors can be beneficial target to unravel the disease pathologies and potential therapeutics.