Biology subjects

Amorim, J.

Publications and source records attributed to Amorim, J..

5 recordsLinked to original sources

bioRxiv2026

Trpv1+ sensory innervation of the salivary gland drives pain and supports saliva secretion

Sensory neurons have been increasingly recognized as vital contributors to deep tissue function. However, how these specialized neurons contribute to salivary gland function remains largely undefined. Here, we uncover a role for trigeminal somatosensory afferents in salivary gland perception and function using in situ-based classification, in vivo calcium imaging, behavioral assays, and targeted ablation. Retrograde labeling from the submandibular gland complex revealed substantial direct innervation from trigeminal neurons. Further categorization confirmed that Trpv1+ sensory neurons provided dense innervation of the Whartons ducts. TRPV1 agonist ductal infusion directly activated gland complex-associated neurons in the trigeminal ganglia and evoked a robust pain phenotype. Targeted Trpv1+ ablation disrupted Whartons ducts structure and dramatically reduced stimulated saliva volume. Our work provides the first evidence that Trpv1+ sensory neurons maintain salivary architecture and are necessary for stimulated saliva production, revealing a vital interoceptive role for direct trigeminal innervation in submandibular gland health.

physiology↗

bioRxiv2026

Assessing Bioactivity and Biointegration of Engineered Salivary Tissue Constructs in a Preclinical Unilateral Fractionated Irradiated Rat Model

Human salivary stem/progenitor cell (hS/PC)-loaded hyaluronic acid (HA)-based hydrogels, termed 3D-salivary tissue constructs (3D-ST), hold great promise for restoring salivary gland function post-radiation injury. Here, we developed a next-generation 3D-ST using heparin-modified HA and bioactive peptide-modified hydrogels. This new formulation enables controlled pre-loading and localized presentation of heparin-binding growth factors prior to surgical implantation, providing opportunities to enhance in vivo hS/PC bioactivity. To model clinically relevant radiation injury, we established an athymic rat model subjected to computed tomography (CT)-guided fractionated radiation, resulting in hallmark features of radiation-induced salivary dysfunction. Over 60-days post-irradiation, glands exhibited progressive loss of acini, increased fibrosis, and disruption of endothelial, neuronal, and myoepithelial compartments. Within this injured environment, a surgical pocket was created to precisely implant 3D-STs to assess graft performance. Fluorescent labeling of the 3D-STs enabled longitudinal tracking post-implantation. Over 14 days, implanted 3D-STs remained structurally stable within irradiated glands, and hS/PCs remained viable without evidence of local inflammatory responses. Compared to non-injured glands, the irradiated microenvironment suppressed hS/PC proliferation and phenotype, indicating alterations in the irradiated local tissue negatively impact hS/PC bioactivity. In addition, host neurovascular migration into the 3D-ST was majorly restricted in irradiated glands, providing new opportunities to enhance biointegration. Overall, this work establishes a reproducible preclinical framework for assessing hydrogel biocompatibility and stability, cell bioactivity, and host-graft biointegration prior to scale up into preclinical large animal models. This study has successfully established a tractable approach for improving 3D-ST formulations to enhance hS/PC expansion, differentiation, and biointegration following implantation into radiation-injured beds.

bioengineering↗

bioRxiv2026

A dual-phase enhancer couples progenitor maintenance and pancreatic lineage stability

Enhancers orchestrate transcriptional programs that control organ development and maintain differentiated cell states, yet how individual enhancers integrate developmental and long-term tissue maintenance logic remains poorly understood. Here, we identify a distal enhancer downstream of ptf1a (z3-DpE) as a regulatory node coupling pancreatic development with acinar cell homeostasis in zebrafish. Deletion of z3-DpE reduces ptf1a expression in pancreatic multipotent progenitor cells (MPCs), leading to depletion of the progenitor pool, altered morphogenesis, and premature exocrine differentiation. Transcriptomic analysis reveals broad repression of proliferation- and morphogenesis-related genes, including Notch pathway components essential for progenitor maintenance. After differentiation, loss of z3-DpE contributes to acinar cell loss, expansion of ductal and endocrine compartments, and disrupted pancreatic architecture. Chromatin-accessibility profiling of purified acinar cells reveals that reduced ptf1a activity leads to widespread remodeling of the acinar chromatin landscape, with decreased accessibility at loci associated with acinar identity and developmental programs, and increased accessibility at sites linked to inflammation, epithelial plasticity, and pancreatic cancer susceptibility. Histopathological analysis shows disorganized acinar tissue with increased duct-like structures and mucinous lesions reminiscent of early pancreatic neoplasia. Thus, z3-DpE safeguards acinar identity by sustaining ptf1a expression and a chromatin landscape that restricts fate instability and pathological plasticity. Our findings demonstrate the mechanistic sufficiency of a single enhancer to coordinate progenitor expansion and long-term lineage stabilization, providing a paradigm for how a developmental regulatory element is redeployed to preserve tissue integrity and suppress disease-associated plasticity.

developmental biology↗

bioRxiv2025

Loss of Vitellogenin Receptor Function Results in Yolk Depletion, Virome Expansion and Reduced Bacterial Load Within the Oocytes of Rhodnius prolixus

The vitellogenin receptor (VgR) mediates yolk protein uptake during oogenesis and is essential for embryogenesis in oviparous species. Here we characterize the single Rhodnius prolixus VgR isoform and uncover an unexpected role in microbial regulation within the reproductive system. The receptor displays a conserved LDLR-like structure and is highly expressed in early oocytes. RNAi-mediated VgR silencing caused defective yolk granule biogenesis, leading to the accumulation of the main yolk protein precursors, Vg and RHBP, in the hemolymph, yet oviposition and fertilization proceeded normally. The resulting eggs were yolk-depleted and non-viable. Remarkably, VgR knockdown reduced bacterial 16S rRNA levels in oocytes while promoting the expansion of several members of the core virome, a phenotype not reproduced by Vg silencing. Neither purified Vg nor changes in immune (defensin) or RNA interference pathways explained the microbial shifts. These findings indicate that VgR governs not only yolk endocytosis but also the trafficking of microbial components into developing oocytes. We propose that VgR contributes to the linking of yolk endocytic dynamics and microbial homeostasis, influencing the balance of microbial components within developing oocytes. This connection broadens the functional scope of the VgR and provides new insight into how vertical transmission processes are shaped in this major Chagas disease vector. Author summaryEgg-laying animals must load their eggs with enough nutrients to support early development. In insects, this process depends on a receptor that brings yolk proteins into the growing egg. Here, we studied this receptor in Rhodnius prolixus, a major vector of Chagas disease, and uncovered an unexpected link between yolk uptake and the microorganisms that enter the egg. When we blocked the receptor, females continued to produce and lay eggs, but these eggs failed to accumulate yolk and could not support embryonic development. Strikingly, the absence of the receptor also shifted the microbial community inside the oocyte: bacterial levels dropped, while several viruses expanded. These changes did not result from differences in yolk proteins, immune activation, or direct antimicrobial effects, indicating that the receptor itself influences microbial entry or persistence in the egg. Our findings reveal that this yolk receptor plays a dual role, providing nutrients and shaping the microbial community that is passed from mother to offspring. This work highlights an unrecognized layer of interaction between reproduction and microbial transmission in an important disease vector, offering new perspectives for understanding and potentially disrupting vertical transmission pathways.

cell biology↗

bioRxiv2024

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD+ can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD+ precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD+ metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD+ boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

pharmacology and toxicology↗