Circadian dynamics of the Zbtb14 protein in the ventral hippocampus are disrupted in epileptic mice

Our previous in silico data indicated an overrepresentation of the ZF5 motif in the promoters of genes in which circadian oscillations are altered in the ventral hippocampus in the pilocarpine model of temporal lobe epilepsy in mice. In this study, we test the hypothesis that the Zbtb14 protein oscillates in the hippocampus in a circadian manner and that this oscillation is disrupted by epilepsy.

We found that Zbtb14 immunostaining is present in the cytoplasm and cell nuclei. Western blot data indicate that the cytoplasmic and nuclear levels of Zbtb14 protein oscillate, but the phase is shifted. The densities of the Zbtb14-immunopositive express circadian dynamics in the ventral hilus and Ca3 but not in the dorsal hilus, Ca3, or the somatosensory cortex. In the pilocarpine model of epilepsy increase in the level of Zbtb14 protein was found at 11 PM, but not at 3 PM compared to controls. Finally, in silico analysis revealed the presence of the ZF5 motif in the promoters of 21 out of 24 genes down-regulated by epileptiform discharges in vitro , many of which are involved in neuronal plasticity. Our data suggest that Zbtb14 may be involved in the circadian dynamic of seizure regulation or brain response to seizure rhythmicity.

Highlights

• the Zbtb14 protein is expressed in neurons in the mouse brain;

• Zbtb14 protein levels oscillate through the circadian cycle in the ventral hippocampus but not in the dorsal hippocampus;

• the oscillations of the Zbtb14 protein occur in both the cytoplasm and nucleus but in a different temporal pattern;

• the circadian dynamics of the Zbtb14 protein are perturbed in epilepsy in an in vivo model of epilepsy;

• numerous genes that are downregulated in the in vitro model of epileptiform discharges have a ZF5 motif in their promoters