Biology subjects

Voronova, A.

Publications and source records attributed to Voronova, A..

3 recordsLinked to original sources

bioRxiv2024

Prefrontal gamma oscillations and fear extinction learning require early postnatal interneuron-oligodendroglia communication

Emerging evidence links oligodendrocyte (OL) lineage cells and myelin to cognitive processes, yet the role of myelination in shaping neuronal networks critical for cognitive tasks remains unknown. We demonstrate in mice that early postnatal GABAergic signaling between interneurons and oligodendrocyte precursor cells (OPCs) is crucial for myelination of parvalbumin (PV) interneurons, which facilitates in vivo low-gamma oscillations in the medial prefrontal cortex (mPFC) and supports fear extinction learning. Disruption of this signaling results in PV interneuron dysmyelination, decreases low-gamma power, and impairs tone fear extinction. These deficits are specific to PV interneuron dysmyelination, as mPFC myelination, high-gamma oscillations and contextual fear extinction are not significantly altered. Increasing PV interneuron activity or enhancing myelination do not reverse the deficits, indicating the long-term consequences of these early myelination impairments. Our findings reveal the role of OPC GABAergic signaling in PV interneuron myelination and mPFC circuit maturation, with lasting impacts on gamma rhythms and cognition. Brief SummaryEarly postnatal interneuron-oligodendroglia communication may shape neuronal networks underlying cognition. Here, the authors show that disrupting this signaling in mice impairs interneuron myelination, gamma rhythms, and fear-related learning.

neuroscience↗

bioRxiv2024

Single-Cell Analysis Reveals Critical Role of Macrophage Epsin in Regulating Origin of Foam Cell in Atherosclerosis

Atherosclerosis is a chronic inflammatory condition characterized by the excessive accumulation of fat and lipid molecules, leading to the formation of foam cells and plaques in arterial walls. Dysfunction of vascular smooth muscle cells (VSMCs), fibroblast, endothelial cells, and macrophages is often associated with this pathology. We found that epsins accelerate atherosclerosis progression in individuals on a Western diet (WD). Using ApoE-deficient (ApoE-/-) and macrophage-specific epsin deletion in ApoE-/- backgrounds (LysM-DKO/ApoE-/-) mice fed a WD for 16 weeks, we observed significantly reduced foam cell formation in LysM-DKO/ApoE-/- mice compared to ApoE-/- mice. Single-cell RNA sequencing identified 20 major cell types, including seven VSMC and five macrophage subtypes. Among the VSMC subtypes, modulating VSMC1 was involved in inflammation and migration, while modulating VSMC2 was associated with VSMC phenotype switching. In atherosclerotic mice, populations of modulating VSMC1, VSMC2, foamy-Trem2, and inflammatory macrophages increased, but significantly decreased in epsin-deficient mice. Modulating VSMC2 transition into macrophages occurred with a probability of 0.57 in ApoE-/- mice, compared to 0.01 in LysM-DKO/ApoE-/- mice. Epsin deletion also reversed endothelial dysfunction and downregulated cholesterol and glucose-mediated signals, as well as inflammatory ligands Il1b and C1qa. Our findings suggest that epsin deletion reduces foam cell formation and rewires VSMC and endothelial functions, offering a novel therapeutic strategy for atherosclerosis.

cell biology↗

bioRxiv2021

Increasing phagocytosis of microglia through targeting CD33 with liposomes displaying glycan ligands

CD33 is an immunomodulatory receptor expressed on microglia and genetically linked to Alzheimers disease (AD) susceptibility. While antibodies targeting CD33 have entered clinical trials to treat neurodegeneration, it is unknown whether the glycan-binding properties of CD33 can be exploited to modulate microglia. Here, we use liposomes that multivalently display glycan ligands of CD33 (CD33L liposomes) to engage CD33. We find that CD33L liposomes increase phagocytosis of cultured monocytic cells and microglia in a CD33-dependent manner. Enhanced phagocytosis strongly correlates with loss of CD33 from the cell surface and internalization of liposomes. Increased phagocytosis by treatment with CD33L liposomes is dependent on a key intracellular signaling motif on CD33 as well as the glycan-binding ability of CD33. These effects are specific to trans engagement of CD33 by CD33L liposomes, as cis engagement through insertion of lipid-linked CD33L into cells produces the opposite effect on phagocytosis. Moreover, intracerebroventricular injection of CD33L liposomes in mice enhances phagocytosis of microglia in a CD33-dependent manner. These results demonstrate that multivalent engagement of CD33 with glycan ligands can modulate microglial cell function.

immunology↗