Biology subjects

Limkar, A. R.

Publications and source records attributed to Limkar, A. R..

3 recordsLinked to original sources

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↗

bioRxiv2025

Ex vivo high-resolution nano-computed tomography imaging reveals spatial architecture of the adult male mouse lower urogenital tract

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms/dysfunction (LUTS/LUTD) in aging men. Over the past 30 years, the prevalence of BPH has increased by 122%, rising from 50.7 million cases in 1990 to 112.5 million in 2021. It is expected that this number will continue to rise over the next 15 years with the global aging population. Although mouse models are invaluable for studying human disease, gross anatomical differences between human and murine prostates complicate their translational relevance for BPH/LUTS research. The purpose of this study was to develop and validate a nanoCT-based imaging approach to enable detailed anatomical analysis of the murine lower urinary tract, with the dual goals of advancing tools for LUTD research and improving the translational relevance of mouse models to human prostate disease. Advancements in nano-computed tomography (nanoCT) have enabled high-resolution characterization of murine organ anatomy, providing new insights into how morphological differences contribute to pathology. To accomplish this, whole lower urogenital tracts from 8-week-old healthy male C57BL/6J mice and microdissected urethras were imaged on a v|tome|x M or nanotom M nano-CT system, respectively. Images were processed for 2D segmentation and subsequent 3D reconstruction using DragonFly 3D World software. Our approach enabled high-resolution visualization and characterization of the murine lower urogenital tract, including the urinary bladder, prostate lobes, seminal vesicles, and ductus deferens, as well as the microscopic ductal architecture of the prostatic urethra. The resulting 3D reconstructions preserved native anatomical relationships and allowed for comparisons between murine and human prostate anatomy. Together, these findings establish a method that can be used for assessing anatomical and morphological changes associated with LUTD development, while also highlighting key anatomical similarities that enhance the translational relevance of mouse models for human prostate disease.

pathology↗

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↗