Biology subjects

Vovk, A.

Publications and source records attributed to Vovk, A..

3 recordsLinked to original sources

bioRxiv2025

Prenatal maternal stress is associated with increased sensitivity to neuropathic pain and sex-specific epigenetic and transcriptomic dynamics in the prefrontal cortex

Prenatal maternal stress (PNS) is a common early-life adversity. PNS has been linked to greater vulnerability to chronic pain in the offspring. PNS results in increased hypersensitivity after Chronic Constriction Injury (CCI) of the sciatic nerve, a common rodent model for chronic neuropathic pain. These behavioral effects are accompanied by altered levels of enzymes that regulate DNA methylation in the frontal cortex. DNA methylation, the addition of a methyl group onto cytosine bases of cytosine-guanine (CpG) sites in the genome, is an epigenetic mechanism by which life experiences can reprogram gene expression. The goal of this study was to identify differentially methylated regions that might contribute to the increased pain sensitivity following nerve injury in adulthood. Prior studies indicate widespread, sex-specific transcriptomic changes and numerous differentially methylated regions (DMRs) in the frontal cortex following PNS and nerve injury. Here we performed genome wide DNA methylation and transcriptome-wide RNAseq analysis in the frontal cortex of male and female mice that underwent PNS, CCI or both. Our analysis revealed sex-dependent changes in DNA methylation and mRNA expression, including in pathways related to neuronal and brain development, axonogenesis and synaptic regulation. The effect of DNA methylation on mRNA expression was tested in a subset of target genes. These studies suggest a role for DNA methylation in embedding increased risk for chronic pain in adulthood associated with early-life adversity.

neuroscience↗

bioRxiv2023

Poly ADP-ribosylation regulates Arc expression and promotes adaptive stress-coping

Rapid adaptation to stressful events is essential for survival and requires acute stress response and stress-coping strategy. Yet, the molecular mechanisms that govern this coping strategy have to be fully discovered. Poly ADP-ribosylation (PARylation) is a post-translational protein modification that plays a vital role in histone modification following neuronal activity and is required for long-term memory formation. Previous studies showed that inhibiting Parp1, the primary enzyme that catalyzes poly ADP-ribose polymers (PAR), impairs long-term memory formation. However, the target genes of Parp1-induced PARylation following acute stress are unknown. Here, we showed that the forced swim test, a well-established acute stress paradigm, induced elevated cortical PARylation and increased the expression of activity-dependent genes in mice. Systemic pharmacological Parp1 inhibition with ABT888 (Veliparib), impaired stress-coping in a second forced swim test done 24 hours later as measured by diminished immobility response. This effect was associated with reduced PARylation of Arc promoter and reduced Arc expression, 1 hour after Parp1 inhibition, suggesting Arc PARylation regulates its expression and hence successful stress-coping behavior.

neuroscience↗

bioRxiv2020

Effects of Sequence Composition and Patterning on the Structure and Dynamics of Intrinsically Disordered Proteins

Unlike the well defined structures of classical natively folded proteins, Intrinsically Disordered Proteins (IDP) and Intrinsically Disordered Regions (IDR) dynamically span large conformational and structural ensembles. This dynamic disorder impedes the study of the relationship between the amino acid sequences of the IDPs and their spatial structures, dynamics, and function. Multiple experimental and theoretical evidence points in many cases to the overall importance of the general properties of the amino acid sequence of the IPDs rather than their precise atomistic details. However, while different experimental techniques can probe aspects of the IDP conformations, often different techniques or conditions offer seemingly contradictory results. Using coarse-grained polymer models informed by experimental observations, we investigate the effects of several key variables on the dimensions and the dynamics of IDPs. The coarse-grained simulations are in a good agreement with the results of atomistic MD. We show that the sequence composition and patterning are well reflected in the global conformational variables such as the radius of gyration and hydrodynamic radius, while the end-to-end distance and dynamics are highly sequence specific. We identify the conditions that allow mapping of highly heterogeneous sequences of IDPs onto averaged minimal polymer models. We discuss the implications of these results for the interpretation of the recent experimental measurements, and for further development of appropriate mesoscopic models of IDPs.

biophysics↗