Biology subjects

Bernier, L.-P.

Publications and source records attributed to Bernier, L.-P..

3 recordsLinked to original sources

bioRxiv2026

Brain pericytes are an oxidative stress-sensitive cell population damaged through ROS-1 dependent TRPA1 activation.

Oxidative stress is a pathological process driven by an imbalance between the production and clearance of reactive oxygen species (ROS). It is a hallmark of numerous brain disorders, driving neuroinflammation, blood-brain barrier (BBB) disruption, and neurodegeneration. Here, we used two-photon microscopy in rodent brain slices to evaluate cell-type vulnerability to oxidative stress. We identified a microvascular cell population displaying pronounced sensitivity to H2O2 and thiol oxidation. These Pdgfr-{beta} expressing cells were identified as pericytes and perivascular fibroblasts. Because pericytes regulate capillary perfusion and BBB integrity, we examined mechanisms driving their injury. Pericyte damage was independent of apoptosis or necroptosis, but required Ca2+ influx. While blocking voltage-gated Ca2+, TRPC, Orai channels was ineffective, inhibitors of TRPA1 channels reduced pericyte damage. Immunostaining and western blotting showed TRPA1 associated with brain capillaries and pericytes. Functionally, TRPA1 regulated uptake of the pericyte-selective marker NeuroTrace, whereas pericyte GCaMP6f imaging demonstrated that TRPA1 was not the primary driver of cytosolic Ca2+ elevations during oxidative stress. These findings establish pericytes as vulnerable targets of oxidative stress and implicate TRPA1 as a mediator of pericyte structural degeneration. This sensitivity to oxidative stress, mediated by ROS-TRPA1 coupling, could contribute to the pericyte stress and degeneration observed in brain pathology.

neuroscience↗

bioRxiv2025

Single cell approaches define the murine leptomeninges:cortical brain interface as a distinct cellular neighborhood comprised of neural and nonneural cell types

The interface between the brain surface and the adjacent meninges is a selective barrier regulating fluid, protein and immune cell exchange between the CNS and periphery. However, the cell types that form this important interface are not yet fully defined. To address this limitation, we have used single cell RNA-sequencing (scRNA-seq) and single cell spatial transcriptomics together with morphological lineage tracing and immunostaining to analyze the adult murine cortex. We show that the cortical interface is comprised of three major cell types, leptomeningeal cells, border astrocytes and tissue-resident macrophages. On the peripheral side the interface is comprised of transcriptionally-distinct PDGFR-positive leptomeningeal mesenchymal cells that are intermingled with macrophages. This leptomeningeal pial layer is lined by a population of transcriptionally-distinct border astrocytes. The interface neighborhood is rich in growth factor mRNAs, including many leptomeningeal ligands predicted to act on both the border astrocytes and macrophages. On the CNS side of the interface is the relatively cell-sparse cortical layer one containing interneurons, microglia, parenchymal astrocytes, oligodendrocyte precursor cells and oligodendrocytes. Except for the border astrocytes, layer one cells are not closely-associated with the interface, suggesting that secreted ligands may be the major way the brain interface communicates with the underlying cortical parenchyma. Thus, our data provide a molecular/cellular resource describing the brain interface cell types and their interactions, thereby enabling future studies asking how this distinct cellular compartment regulates CNS:periphery interactions. Significance StatementRecent years have seen significant progress in identifying the diverse cell types within the meningeal space. However, the mechanisms by which these cells interact with glial and neuronal cells in layer one of the adult murine cortex remain poorly understood. During development, communication between radial precursors and meningeal layers is crucial for proper brain formation, but the role of this interaction in adulthood is still unclear. Additionally, how resident immune cells in the leptomeningeal space signal to layer one cortical cells or meningeal mesenchymal cells during homeostasis remains an open question. Understanding the identity, location, and interactions of these cells is essential for unraveling the complex dynamics at this critical brain interface.

neuroscience↗

bioRxiv2021

Age related susceptibility to grey matter demyelination and neurodegeneration is associated with meningeal neutrophil accumulation in an animal model of Multiple Sclerosis

People living with multiple sclerosis (MS) experience episodic central nervous system (CNS) white matter lesions instigated by autoreactive T cells. With age, MS patients show evidence of grey matter demyelination and experience devastating non-remitting symptomology. What drives progression is unclear and has been hampered by the lack of suitable animal models. Here we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induces a non-remitting clinical phenotype that is associated with persistent leptomeningeal inflammation and cortical pathology in old, but not young SJL/J mice. While the quantity and quality of T cells did not differ in the brains of old vs young EAE mice, an increase in neutrophils and a decrease in B cells was observed in the brains of old mice. Neutrophils were also found in the leptomeninges of a subset of progressive MS patient brains that showed evidence of leptomeningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and grey matter pathology are dictated by age and associated with other immune cells such as neutrophils.

immunology↗