Biology subjects

Lukasiuk, K.

Publications and source records attributed to Lukasiuk, K..

4 recordsLinked to original sources

bioRxiv2024

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. HighlightsO_LIthe Zbtb14 protein is expressed in neurons in the mouse brain; C_LIO_LIZbtb14 protein levels oscillate through the circadian cycle in the ventral hippocampus but not in the dorsal hippocampus; C_LIO_LIthe oscillations of the Zbtb14 protein occur in both the cytoplasm and nucleus but in a different temporal pattern; C_LIO_LIthe circadian dynamics of the Zbtb14 protein are perturbed in epilepsy in an in vivo model of epilepsy; C_LIO_LInumerous genes that are downregulated in the in vitro model of epileptiform discharges have a ZF5 motif in their promoters C_LI

neuroscience↗

bioRxiv2024

miR-155-5p/miR-674-3p presence in peripheral blood leukocytes and relative proportion of white blood cell types as biomarkers of asymptomatic and symptomatic phases of temporal lobe epilepsy

Epilepsy frequently develops as a result of brain insult, for example, brain injury or stroke. Currently, there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed white blood cell subpopulations containing miR-155-5p and miR-674-3p, in control and stimulated animals and in control and symptomatic or asymptomatic animals in the amygdala stimulation model. The first proposed early biomarker of epilepsy is the relative proportion of CD45RA+ B cells containing miR-155-5p and/or miR-674-3p. Others are increased number of CD45RA+ B cells containing either miR-155-5p or miR-155-5p and miR-674-3p together or decreased number of CD161+ NK cells not containing miR-155-5p nor miR-674-3p. Additionally, we found that the decreased number of CD4+ T cells can be used as a potential biomarker for identifying epileptic animals with symptomatic epilepsy.

neuroscience↗

bioRxiv2018

SorCS2 controls functional expression of amino acid transporter EAAT3 to protect neurons from oxidative stress and epilepsy-induced pathology

The family of VPS10P domain receptors emerges as central regulator of intracellular protein sorting in neurons with relevance for various brain pathologies. Here, we identified a unique role for the family member SorCS2 in protection of neurons from oxidative stress and from epilepsy-induced cell death. We show that SorCS2 acts as sorting receptor that targets the neuronal amino acid transporter EAAT3 to the plasma membrane to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Absence of SorCS2 activity causes aberrant transport of EAAT3 to lysosome for catabolism and impairs cysteine uptake. As a consequence, SorCS2-deficient mice exhibit oxidative brain damage that coincides with enhanced neuronal cell death and increased mortality during epilepsy. Our findings highlight a protective role for SorCS2 in neuronal stress response and provide an explanation for upregulation of the receptor seen in surviving neurons of the human epileptic brain.

neuroscience↗

bioRxiv2017

The circadian hippocampus and its reprogramming in epilepsy: impact for chronotherapeutics

Gene and protein expression displays circadian oscillations in numerous body organs. These oscillations can be disrupted in diseases, thus contributing to the disease pathology. Whether the molecular architecture of cortical brain regions oscillates daily and whether these oscillations are modified in brain disorders is less understood. We identified 1200 daily oscillating transcripts in the hippocampus of control mice. More transcripts (1600) were oscillating in experimental epilepsy, with only one fourth oscillating in both conditions. Proteomics confirmed these results. Metabolic activity and targets of antiepileptic drugs displayed different circadian regulation in control and epilepsy. Hence, the hippocampus, and perhaps other cortical regions, shows a daily remapping of its molecular landscape, which would enable different functioning modes during the night/day cycle. The impact of this remapping in brain pathologies needs to be taken into account not only to study their mechanisms, but also to design drug treatments and time their delivery.

neuroscience↗