Biology subjects

Saravanan, A.

Publications and source records attributed to Saravanan, A..

4 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↗

bioRxiv2025

Delayed forebrain excitatory and inhibitory neurogenesis inSTRADA-related megalencephaly via mTOR hyperactivity

Biallelic pathogenic variants in STRADA, an upstream regulator of the mechanistic target of rapamycin (mTOR) pathway, result in megalencephaly, drug-resistant epilepsy, and severe intellectual disability. This study explores how mTOR pathway hyperactivity alters cell fate specification in dorsal and ventral forebrain development using STRADA knock-out human stem cell derived brain organoids. In both dorsal and ventral forebrain STRADA knock-out organoids, neurogenesis is delayed, with a predilection for progenitor renewal and proliferation and an increase in outer radial glia. Ventrally, interneuron subtypes shift to an increase in neuropeptide-Y expressing cells. Inhibition of the mTOR pathway with rapamycin results in rescue for most phenotypes. When mTOR pathway variants are present in all cells of the developing brain, overproduction of interneurons and altered interneuron cell fate may underlie mechanisms of megalencephaly, epilepsy, and cognitive impairment. Our findings suggest mTOR inhibition during fetal brain development as a potential therapeutic strategy in STRADA deficiency.

neuroscience↗

bioRxiv2025

Custom-Built Electrodes Perform Comparably to a Discontinued Commercial Electrode for Neuromuscular Electrical Stimulation in Mice

ObjectiveA commercial electrode used for transcutaneous neuromuscular electrical stimulation (NMES) in mice is no longer available. In response, we developed two low- cost, customizable alternatives--a 3D-Printed Electrode and a Pen Electrode assembled from off-the-shelf jumper wire components--and evaluated their performance relative to the discontinued commercial standard. MethodsWe conducted in vivo NMES of the left hindlimb ankle dorsiflexors in C57BL/6J mice using three electrode types: a Simple Electrode (previously available as BS4 50-6824, Harvard Apparatus), our novel 3D-Printed Electrode, and our novel Pen Electrode. Contractile torque was recorded during twitch and tetanic contractions, and electrode performance was evaluated based on peak torque values. A repeated measures ANOVA was used to compare torque generated by each animal for the three different types of electrodes. ResultsBoth custom electrodes generated twitch and tetanic responses comparable to those of the Commercial electrode. No statistically significant differences were observed in peak torque values in either twitch (p = 0.181) or tetany (p = 0.438). ConclusionCustom-built 3D-printed and Pen-style electrodes offer low-cost, accessible alternatives to discontinued commercial devices for murine NMES studies. These tools can facilitate continued use of electrical stimulation protocols in preclinical neuromuscular research.

physiology↗

bioRxiv2025

In-vivo Efficacy of a Phage Cocktail Therapy that Targets ESBL-producing Klebsiella Urinary Tract Infections Clinical Isolates

Uropathogenic Klebsiella pneumoniae strains, are of major concern of with respect to antimicrobial resistance, which has sparked interest in phage therapy as an alternative, or compliment to antibiotics. However, very limited in vivo data on phage therapy safety and efficacy for treating UTIs is available. To address this, we developed a model to test these parameters for a phage cocktail optimised for Extended Spectrum Beta-Lactamases (ESBL)-producing Klebsiella UTI strains. Female C57BL/6J mice were infected with K. pneumoniae Top52 then received a single dose of the purified therapeutic phages, with observations over seven days. Results showed a significant reduction of bacterial burden in urine, bladder, and kidney samples starting from 4 h post-treatment until Day 7. Phage treatment also reduced local inflammation within the bladder. Additionally, cytokine profile demonstrated an increase in anti-inflammatory IL-10 and a decrease in pro-inflammatory IL-6, indicating a synergy between phage and the host immune response.

microbiology↗