Biology subjects

Ravi, P.

Publications and source records attributed to Ravi, P..

4 recordsLinked to original sources

bioRxiv2025

Exercise-induced plasma-derived extracellular vesicles increase adult hippocampal neurogenesis

Aerobic exercise enhances cognition in part by increasing adult hippocampal neurogenesis, angiogenesis, and astrogliogenesis. Since hippocampal atrophy is a hallmark of several neurological and psychiatric conditions--including depression, PTSD, Alzheimers disease, and aging--understanding the mechanisms by which exercise increases neurogenesis has broad therapeutic relevance. One potential mechanism involves extracellular vesicles (EVs), lipid bilayer-enclosed particles released by multiple tissues during exercise that transport bioactive molecular cargo to distant organs, including the brain. In this study, we tested whether plasma-derived EVs from exercising mice (ExerVs) are sufficient to promote hippocampal neurogenesis, astrogliogenesis, and vascular density in sedentary mice. EVs were isolated from the plasma of sedentary or exercising C57BL/6J mice and injected intraperitoneally into sedentary recipients twice weekly for four weeks. To evaluate reproducibility, the study was conducted across two independent cohorts using identical procedures. ExerV-treated mice showed a significant increase in BrdU-positive cells in the granule cell layer compared to both PBS- and SedV-treated controls in both cohorts. Approximately 90% of these cells co-expressed NeuN, indicating neuronal differentiation, while 6% co-expressed S100{beta}, indicating astrocyte generation. No changes were observed in vascular density across groups. These findings provide initial evidence that systemically delivered exercise-derived EVs can enhance hippocampal neurogenesis and astrogliogenesis in sedentary mice. This proof-of-concept work supports further investigation into ExerVs as a potential therapeutic strategy for conditions associated with hippocampal atrophy. HighlightsO_LIExerVs increase hippocampal neurogenesis and astrogliogenesis in sedentary mice C_LIO_LIExerVs do not affect hippocampal vascular area C_LIO_LICirculating ExerVs are sufficient to recapitulate key brain benefits of exercise C_LI

neuroscience↗

bioRxiv2025

SoxB1 family members inhibit Wnt signaling to promote maturation and deposition of stable neuromasts by the zebrafish Posterior Lateral Line primordium

Periodic formation of protoneuromasts within the migrating zebrafish Posterior Lateral Line primordium serves as a model for understanding steps that determine the self-organization of organ systems in development. Protoneuromast formation is initiated by Fgf signaling at the trailing zone of the migrating primordium in response to Fgfs produced by Wnt active cells in a leading zone. Progressive restriction of an initially broad Wnt signaling domain to a smaller leading zone allows new Fgf signaling-dependent protoneuromasts to form in the wake of the shrinking Wnt system. We show Sox2 and Sox3 are expressed in nascent and maturing protoneuromasts in a trailing part of the primordium in a pattern that is complementary to Wnt activity in a leading domain, where Sox1a, is expressed. Together, these SoxB1 factors help inhibit Wnt signaling to determine effective maturation of trailing protoneuromasts and the timely deposition of stable neuromasts. Using dkk1b and atoh1b to monitor initiation and subsequent maturation of protoneuromasts, respectively, we show how Wnt signaling regulates the pace of protoneuromast maturation in the migrating primordium, and how its inhibition by SoxB1 family members ensures maturation and deposition of stable neuromasts. Together, our observations define three steps in the periodic formation of neuromasts: first, polarization of Wnt activity in the primordium; second, pattern forming step that determines periodic formation of protoneuromasts in the context of polarized Wnt activity; and third, inhibition of Wnt signaling, which is essential for stabilizing nascent neuromasts formed in the earlier pattern forming stage.

developmental biology↗

bioRxiv2021

Integrative Clinical and Molecular Characterization of Translocation Renal Cell Carcinoma

ABSTRACTTranslocation renal cell carcinoma (tRCC) is an aggressive and poorly-characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 tRCC patients identified across multiple genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to many targeted therapies. Consistently, we find that outcomes for tRCC patients treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKI) are worse than those treated with immune checkpoint inhibition (ICI). Multiparametric immunofluorescence confirmed the presence of CD8 + tumor-infiltrating T cells compatible with a clinical benefit from ICI and revealed an exhaustion immunophenotype distinct from clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.

cancer biology↗

bioRxiv2018

FMRFa receptor stimulated Ca2+ signals alter the activity of flight modulating central dopaminergic neurons in Drosophila melanogaster

Neuropeptide signaling influences animal behavior by modulating neuronal activity and thus altering circuit dynamics. Insect flight is a key innate behavior that very likely requires robust neuromodulation. Cellular and molecular components that help modulate flight behavior are therefore of interest and require investigation. In a genetic RNAi screen for G-protein coupled receptors that regulate flight bout durations, we earlier identified several receptors, including the receptor for the neuropeptide FMRFa (FMRFaR). To further investigate modulation of insect flight by FMRFa we generated CRISPR-Cas9 mutants in the gene encoding the Drosophila FMRFaR. The mutants exhibit significant flight deficits with a focus in dopaminergic cells. Expression of a receptor specific RNAi in adult central dopaminergic neurons resulted in progressive loss of sustained flight. Further, genetic and cellular assays demonstrated that FMRFaR stimulates intracellular calcium signaling through the IP3R and helps maintain neuronal excitability in a subset of dopaminergic neurons for positive modulation of flight bout durations.\n\nAuthor summaryNeuropeptides play an important role in modulating neuronal properties such as excitability and synaptic strength and thereby influence innate behavioral outputs. In flying insects, neuromodulation of flight has been primarily attributed to monoamines. In this study, we have used the genetically amenable fruit fly, Drosophila melanogaster to identify a neuropeptide receptor that is required in adults to modulate flight behavior. We show from both knockdown and knockout studies that the neuropeptide receptor, FMRFaR, present on a few central dopaminergic neurons, modulates the duration of flight bouts. Overexpression of putative downstream molecules, the IP3R, an intracellular Ca2+-release channel, and CaMKII, a protein kinase, significantly rescue the flight deficits induced by knockdown of the FMRFaR. Our data support the idea that FMRFaR and CaMKII help maintain optimal membrane excitability of adult dopaminergic neurons required to sustain longer durations of flight bouts. We speculate that the ability to maintain longer flight bouts in natural conditions enhances the individuals capacity to search and reach food sources as well as find sites suitable for egg laying.

genetics↗