Biology subjects

Bukovac, A.

Publications and source records attributed to Bukovac, A..

3 recordsLinked to original sources

bioRxiv2025

Disruption of the ganglioside-PMCA-Np nexus leads to impaired calcium homeostasis in glioblastoma

Glioblastoma (GBM), an exceedingly invasive brain tumor, is characterized by the disruption of multiple signaling pathways, particularly those governing calcium homeostasis. Additionally, cell membranes in GBM exhibit altered lipidomic profiles, especially complex sialoglycans gangliosides, which affect plasma membranes both structurally and functionally. In this work we show a disruption of a plasma membrane molecular triad composed of gangliosides, neuroplastin (Np), and plasma membrane calcium ATPase (PMCA) in GBM, leading to a severely diminished PMCA activity. Our transcriptomic, epigenetic, proteomic, lipidomic, and in silico analyses consistently demonstrated downregulation of Np and PMCA isoforms both at mRNA and protein levels in our GBM cohort, in agreement with a broader trend observed in public datasets. Analysis of the uniquely changed GBM ganglioside profile in the context of PMCA and Np expression and PMCA activity reveals GD3 as a key molecular determinant of reduced PMCA activity in GBM samples. In contrast, GD1b, necessary for optimal PMCA function in healthy tissue, is significantly reduced in GBM. Our findings establish the gangliosides-PMCA-Np nexus as a crucial complex involved in calcium signaling in GBM, contributing to GBM etiology and progression.

neuroscience↗

bioRxiv2023

The Impact of subicular VIP-expressing interneurons on seizure dynamics in temporal lobe epilepsy: Insights from preclinical models

The subiculum, a key output region of the hippocampus, is increasingly recognized as playing a crucial role in seizure initiation and spread. The subiculum consists of glutamatergic pyramidal cells, which show alterations in intrinsic excitability in the course of epilepsy, and multiple types of GABAergic interneurons, which exhibit varying characteristics in epilepsy. In this study, we aimed to assess the role of the vasoactive intestinal peptide interneurons (VIP-INs) of the ventral subiculum in the pathophysiology of temporal lobe epilepsy. We observed that an anatomically restricted inhibition of VIP-INs of the ventral subiculum was sufficient to reduce seizures in the intrahippocampal kainic acid model of epilepsy, changing the circadian rhythm of seizures, emphasizing the critical role of this small cell population in modulating TLE. As we expected, permanent unilateral or bilateral silencing of VIP-INs of the ventral subiculum in non-epileptic animals did not induce seizures or epileptiform activity. Interestingly, transient activation of VIP-INs of the ventral subiculum was enough to increase the frequency of seizures in the acute seizure model. Our results offer new perspectives on the crucial involvement of VIP-INs of the ventral subiculum in the pathophysiology of TLE. Given the observed predominant disinhibitory role of the VIP-INs input in subicular microcircuits, modifications of this input could be considered in the development of therapeutic strategies to improve seizure control.

neuroscience↗

bioRxiv2018

Comparable genomic copy number aberrations differ across astrocytoma malignancy grades

Malignancy grades of astrocytomas were analyzed for copy number aberrations by aCGH. Altogether 1438 CNA were found of which losses prevailed. We searched for regions that are more likely to drive cancer pathogenesis with Bioconductor package and Genomic Identification of Significant Targets in Cancer. On our total sample significant deletions affected 14 chromosomal regions, out of which deletions at 17p13.2, 9p21.3, 13q12.11, 22q12.3 remained significant even at 0.05 q-value. When divided to malignancy groups, the regions identified as significantly deleted in high grades were: 9p21.3; 17p13.2; 10q24.2; 14q21.3; 1p36.11 and 13q12.11, while amplified were: 3q28; 12q13.3 and 21q22.3. Low grades comprised significant deletions at 3p14.3; 11p15.4; 15q15.1; 16q22.1; 20q11.22 and 22q12.3 indicating their involvement in early stages of tumorigenesis. Significantly enriched pathways brought by DAVID software were PI3K-Akt, Cytokine-cytokine receptor, NODlike receptor, Jak-STAT, RIG-II-like receptor and Toll-like receptor pathways. HPV and herpex simplex infection and inflammation pathways were also represented. Present study brings new data to astrocytoma research amplifying the wide spectrum of changes which could help us identify the regions critical for tumorigenesis.

cancer biology↗