Biology subjects

Vrba, S. M.

Publications and source records attributed to Vrba, S. M..

4 recordsLinked to original sources

bioRxiv2026

Ethmoid bone marrow region modulates lymphoid activation and differentiation with distinct myeloid profile in neuroinflammation

The skull bone marrow axis has recently emerged as an important source of immune cells during neuroinflammation, including in the experimental autoimmune encephalomyelitis (EAE) , the mouse model of multiple sclerosis. The cribriform plate bone marrow (cpBM), is a portion of the ethmoid bone of the skull of mice, and is positioned next to nasal regions. At the cribriform plate olfactory nerves pass through the skull and recent evidence supports that it represents an important immune niche with links to CSF outflow and connections to cpBM. Previous data supports cellular composition of the ethmoid bone marrow in mice is altered in neuroinflammation suggesting it senses inflammatory cues, but the exact nature of these changes is still unclear. Here using scRNAseq and flow cytometry of the ethmoid bone marrow region we test how the region responds to EAE. In addition we also compare the cpBM region with systemic bone marrow in the femur to understand region specific differences. We report that neuroinflammation creates a regulatory response at these sites and implicates the cpBM in controlling these effects. A better understanding of the cribriform niche may offer new treatments for neuroinflammatory disease

immunology↗

bioRxiv2026

Amyloid-beta is present in the spinal cord of APP/PS1 mice and may contribute to neuropathology manifesting as lower urinary tract dysfunction

Urinary incontinence (UI) is a common and debilitating comorbidity in Alzheimers disease (AD), yet its underlying pathophysiology remains poorly defined. While UI in dementia has traditionally been attributed to functional impairment, emerging clinical and urodynamic data suggest that neurologic mechanisms may contribute to lower urinary tract dysfunction in this population. Here, we investigated urinary function and neuropathological changes in aged APP/PS1 mice (AD mice), a widely used model of amyloid pathology. Using functional voiding assays, we identified a pattern of urinary dysfunction characterized by increased urinary frequency, small-volume voiding, shortened void duration, and reduced bladder compliance in the absence of bladder outlet obstruction or gross changes in bladder or prostate morphology. These findings are most consistent with a storage-phase abnormality accompanied by impaired voiding coordination rather than classic detrusor overactivity or underactivity. We examined spinal cord and peripheral components involved in bladder innervation and identified amyloid-beta deposition throughout the thoracolumbar and lumbosacral spinal cord, dorsal root ganglia, ventral roots, cauda equina, and associated meningeal structures in AD mice. Importantly, amyloid deposition was accompanied by reduced expression of vesicular acetylcholine transporter and decreased neuronal activation in bladder-innervating pathways, without evidence of increased apoptosis. Taken together, these data demonstrate that AD mice develop a mixed lower urinary tract dysfunction phenotype associated with amyloid-beta deposition and altered neuronal signaling within the spinal cord and peripheral micturition pathways. These findings support a neurogenic contribution to urinary dysfunction in AD and highlight the spinal cord as a novel site of pathology that may influence urinary symptoms in Alzheimers dementia.

neuroscience↗

bioRxiv2026

Cribriform Plate Microenvironment Assembles a Suppressive Myeloid Network during EAE-induced Neuroinflammation

During neuroinflammation, CD11c+CD11b+ myeloid cells accumulate at the cribriform plate, a key cerebrospinal fluid (CSF) and antigen outflow site in mice. At this site, podoplanin (PDPN)-expressing cells, including lymphatic vessels and meningeal layers, expand to create a distinct drainage microenvironment. In this study we sought to characterize myeloid cells which populate this region using a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Utilizing a combination of immunohistochemistry, flow cytometry, and scRNAseq, we report that macrophages and dendritic cells (DCs) from this region display unique expressional signatures related to tolerance, cell death, and reduced inflammatory profile. Together this data supports that myeloid retention at the cribriform plate and olfactory bulb meninges promotes a local immunosuppressive environment.

immunology↗

bioRxiv2025

Amyloid-beta deposition and reduced drainage at the cribriform plate lymphatics in APP/PS1 mouse model of Alzheimer's Disease

Alzheimers disease (AD) is the most common cause of dementia, leading to substantial personal, economic, and medical costs to patients and society; it is characterized by the build-up of toxic amyloid-beta (A{beta}) and hyperphosphorylated tau. It is crucial to the health of the brain that these proteins are processed or drained effectively, but mounting research has shown that in AD pathology there is dysfunction in the ability of the brain to effectively clear pathological A{beta} and tau. In this report, we detail the involvement of one important brain drainage pathway and potential site of A{beta} clearance, the cribriform plate lymphatics, in 24-month old APP/PS1 mice. We show that cerebrospinal fluid (CSF) efflux is decreased across the cribriform plate area utilizing multiple methods. Moreover, we demonstrate that A{beta} aggregates at the cribriform plate - coating surface of olfactory bulbs (OB), olfactory nerve (ON) bundles, and cribriform plate lymphatic endothelial cells (cpLECs). At 24-months, APP/PS1 mice have increased CD45+ cell infiltration and decreased LYVE-1+ vessel area at the cribriform plate, suggesting local inflammation and lymphatic atrophy. Additionally, cpLECs have higher expression of caspase-3 suggesting the decreased LYVE-1 area is due to cellular toxicity resulting in apoptosis. This study demonstrates that the cribriform plate is an important area for further research elucidating its contribution to AD disease pathogenesis.

neuroscience↗