Biology subjects

Gomez, R.

Publications and source records attributed to Gomez, R..

At least 19 recordsLinked to original sources

bioRxiv2026

AEGIS reveals epitope- and clone-resolved convergence of CNS B and T cell autoreactivity in ROHHAD

Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.

immunology↗

bioRxiv2026

Episodic and semantic memory contributions to imagination and creativity

The ability to generate novel creative ideas (divergent thinking) is closely linked with our ability to imagine novel future events (episodic simulation). Here, we employed an individual differences approach to examine whether divergent thinking and episodic simulation are differentially associated with episodic and semantic retrieval ability. In response to object word cues, participants generated meanings and definitions (semantic memory), remembered a past event (episodic memory), imagined a novel future event (episodic simulation), or generated novel uses (divergent thinking). Replicating previous findings, divergent thinking ability was predicted by the number of episodic details generated during episodic simulation. When directly comparing episodic and semantic memory, the strongest predictor of divergent thinking was semantic memory. In contrast, episodic simulation ability was predicted by both episodic and semantic memory. We interpret these findings as support for the semantic scaffold hypothesis of imagination, according to which semantic memory provides the necessary scaffold or framework for flexible expressions of cognition such as divergent thinking and episodic simulation. As episodic simulation, relative to divergent thinking, was associated with both episodic and semantic retrieval, these findings are taken to reflect common reliance on event construction processes recruited during both episodic remembering and imagining.

neuroscience↗

bioRxiv2026

A Quantitative Model for RhD-Negative Allele Frequency Peaks in Ibero Berber Populations via Synergistic Selection

The RhD-negative blood type reaches its global frequency peak in the Basque population ([~]30-35%), with a secondary peak in isolated Berber groups ([~]15-20%). This discontinuous distribution challenges models based solely on demography or drift. We propose a quantitative model in which allele frequency dynamics are shaped by conditional synergistic selection operating within a unique eco-evolutionary niche. Our framework synthesizes archaeogenomic data to show that admixture between indigenous Western Hunter-Gatherers (carrying a high-frequency RHD deletion) and incoming Neolithic farmers (carrying the SLC24A5 allele) in Iberia generated statistical associations between these unlinked loci. Population-genetic modeling indicates that selection acting on this multi-locus genotype combination can drive co-amplification of both alleles. We argue that this process was maximized in the proto-Basque region--a biocultural refuge characterized by geographic isolation, resource stability, and reduced effective cost of Hemolytic Disease of the Newborn. Subsequent Neolithic gene flow across the Strait of Gibraltar provides a parsimonious mechanism for the shared European RHD deletion observed in Berber populations. Forward-time Wright-Fisher simulations in a structured three-deme framework demonstrate that models incorporating synergistic selection robustly reproduce the observed Ibero-Berber discontinuity across a broad region of parameter space, whereas drift-only models achieve similar outcomes only under comparatively restricted parameter configurations. Parsimony volume comparisons quantify this difference in robustness. Additional deterministic and finite-population simulations confirm that the inferred parameter regime permits directional amplification under both mean-field and stochastic reproduction. Together, these results provide a testable evolutionary framework integrating genetics, environmental history, and epidemiology to explain one of the most striking allele-frequency outliers in human populations.

genetics↗

bioRxiv2024

Translocations can drive expression changes of multiple genes in regulons covering entire chromosome arms

Translocations have largely been implicated in tumor development. However, beyond the consequences of aberrant gene expression near the breakpoint, their effects remain unexplored. In this work, we characterize the interplay between translocations, chromatin organization and gene expression using mantle cell lymphoma (MCL) as a model. We show that in vitro induced MCL-associated translocations can drive transcriptional changes at entire chromosome arms affecting multiple genes in a regulon-like fashion. Additionally, overexpressed genes in MCL patients are enriched in the exact same genomic regions, further underlining its potential relevance for lymphomagenesis. Moreover, we demonstrate a clear link between the translocation-induced transcriptional alterations and genome organization, with genes most susceptible to change expression residing in pre-existing long-range interacting loops spanning 50 megabases. The translocation places the strong immunoglobulin enhancer into this loop, allowing the spread of its regulatory potential over the entire affected chromosome arm. Finally, we show that translocation-induced effects mainly represent expression enhancement of genes already active prior to translocation formation, highlighting the importance of the epigenetic state of the cell in which this initial hit occurs. In summary, we show that translocations can induce ample, simultaneous gene expression changes affecting entire chromosome arms, representing an important new mechanism for tumorigenesis.

cancer biology↗

bioRxiv2024

Antigen-specificity of clonally-enriched CD8+ T cells in multiple sclerosis

CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naive MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. These findings shed vital insight into the role of CD8+ T cells in MS and pave the way towards disease biomarkers and therapeutic targets. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/611010v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a0b738org.highwire.dtl.DTLVardef@5cf5c2org.highwire.dtl.DTLVardef@10abdccorg.highwire.dtl.DTLVardef@32c7b2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical SummaryC_FLOATNO Created in BioRender. Sabatino, J. (2024) BioRender.com/e66l598 C_FIG

immunology↗

bioRxiv2024

Evaluation of behavioral and neurochemical changes induced by carbofuran in zebrafish (Danio rerio)

Carbofuran (CF) is a carbamate class pesticide, widely used in agriculture for pest control in crops. On the other hand, CF is also detected as a contaminant in food and water sources. This pesticide has high toxicity in non-target organisms, and its presence in the environment poses a threat to the ecosystem. Research has revealed that this pesticide acts as an inhibitor of acetylcholinesterase (AChE), inducing an accumulation of acetylcholine in the brain. Consequently, this leads to the emergence of a cholinergic syndrome and various detrimental effects on human health. Nonetheless, our understanding of CF impact on the central nervous system remains elusive. Therefore, this study aimed to investigate the effects of CF on behavioral and neurochemical parameters in adult zebrafish. The animals were exposed for 96 hours to different concentrations of CF (5, 50, and 500 {micro}g/L) and subjected to behavioral assessments in the novel tank test (NTT) and social preference test (SPT). Subsequently, they were euthanized, and their brains were used to evaluate neurochemical markers associated with oxidative stress and AChE levels. In the NTT and SPT, CF did not alter the evaluated behavioral parameters. Furthermore, CF did not affect the levels of AChE, non-protein sulfhydryl groups, and thiobarbituric acid reactive species in the zebrafish brain. However, further research is needed regarding the environmental exposure of this compound to non-target organisms.

neuroscience↗

bioRxiv2024

Elucidation of neuronal activity in mouse models of TMJ injury by in vivo GCaMP Ca2+ imaging of intact trigeminal ganglion neurons

Patients with temporomandibular disorders (TMD) typically experience facial pain and discomfort or tenderness in the temporomandibular joint (TMJ), causing disability in daily life. Unfortunately, existing treatments for TMD are not always effective, creating a need for more advanced, mechanism-based therapies. In this study, we used in vivo GCaMP3 Ca2+ imaging of intact trigeminal ganglia (TG) to characterize functional activity of the TG neurons in vivo, specifically in TMJ animal models. This system allows us to observe neuronal activity in intact anatomical, physiological, and clinical conditions and to assess neuronal function and response to various stimuli. We observed a significant increase in spontaneously and transiently activated neurons responding to mechanical, thermal, and chemical stimuli in the TG of forced mouth open (FMO) mice. An inhibitor of the CGRP receptor significantly attenuated FMO-induced facial hypersensitivity. In addition, we confirmed the attenuating effect of CGRP antagonist on FMO-induced sensitization by in vivo GCaMP3 Ca2+ imaging of intact TG. Our results contribute to unraveling the role and activity of TG neurons in the TMJ pain animal models of TMD, bringing us closer understanding the pathophysiological processes underlying TMD. Our study also illustrates the utility of in vivo GCaMP3 Ca2+ imaging of intact TG for studies aimed at developing more targeted and effective treatments for TMD.

neuroscience↗

bioRxiv2023

Probabilistic Coverage of the Frontal Aslant Tract in Young Adults: Insights into Individual Variability, Lateralization, and Language Functions

The frontal aslant tract (FAT) is a crucial neural pathway of language and speech, but little is known about its connectivity and segmentation differences across populations. In this study, we utilized diffusion MRI automatic tractography to investigate the probabilistic coverage of the FAT in a large sample of 1065 young adults. Our primary goal was to reveal individual variability and lateralization of FAT and its structure-function correlations in language processing. Our results showed that the left anterior FAT exhibited the most substantial individual differences, particularly in the superior and middle frontal gyrus, with greater variability in the superior than the inferior region. Furthermore, we found significant left lateralization in FAT, with a greater difference in innervation coverage in the inferior and posterior portions. Additionally, our analysis revealed a significant correlation between the size of left FAT inferior innervation areas and Picture Vocabulary function, highlighting the structural and functional importance of the left FAT in language processing. In comparison, the anisotropy of FAT did not show significant correlation. Overall, our study provides valuable insights into individual and population differences in FAT connectivity and segmentation and sheds light on its critical role in language functions.

neuroscience↗

bioRxiv2023

Divergent patterns of meiotic double strand breaks and synapsis initiation dynamics suggest an evolutionary shift in the meiosis program between American and Australian marsupials

In eutherian mammals, hundreds of programmed DNA double-strand breaks (DSBs) are generated at the onset of meiosis. The DNA damage response is then triggered. Although the dynamics of this response is well studied in eutherian mammals, recent findings have revealed different patterns of DNA damage signaling and repair in marsupial mammals. To better characterize these differences, here we analyzed synapsis and the chromosomal distribution of meiotic DSBs markers in three different marsupial species (Thylamys elegans, Dromiciops gliorides, and Macropus eugenii) that represent South American and Australian Orders. Our results revealed inter-specific differences in the chromosomal distribution of DNA damage and repair proteins, which were associated with differing synapsis patterns. In the American species T. elegans and D. gliroides, synapsis progressed exclusively from the chromosomal ends towards interstitial regions. This was accompanied by sparse H2AX phosphorylation, mainly accumulating at chromosomal ends, which appeared conspicuously polarized in a bouquet configuration at early stages of prophase I. Accordingly, RAD51 and RPA were mainly localized at chromosomal ends throughout prophaseI in both American marsupials, likely resulting in reduced recombination rates at interstitial positions. In sharp contrast, synapsis initiated at both interstitial and distal chromosomal regions in the Australian representative M. eugenii, {gamma}H2AX had a broad nuclear distribution, and RAD51 and RPA foci displayed an even chromosomal distribution. Given the basal evolutionary position of T. elegans, it is likely that the meiotic features reported in this species represent an ancestral pattern in marsupials and that a shift in the meiotic program occurred after the split of D. gliroides and the Australian marsupial clade. Our results open intriguing questions about the regulation and homeostasis of meiotic DSBs in marsupials. The low recombination rates observed at the interstitial chromosomal regions in American marsupials can result in the formation of large linkage groups, thus having an impact in the evolution of their genomes.

genetics↗

bioRxiv2022

The male mouse meiotic cilium emanates from the mother centriole at zygotene prior to centrosome duplication

Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in the airways and reproductive system, among others. Instead, primary cilia function as cell type-dependent sensory organelles, detecting chemical, mechanical or optical signals from the extracellular environment. Cilia dysfunction is associated with genetic diseases called ciliopathies, and with some types of cancer. Cilia have been recently identified in zebrafish gametogenesis as an important regulator of the bouquet conformation and recombination. However, there is very little information about the structure and functions of cilia in mammalian meiosis. Here we describe the presence of cilia in male mouse meiotic cells. These solitary cilia form transiently in 20% of zygotene spermatocytes and reach considerable lengths (up to 15 m). CEP164 and CETN3 localization studies indicate that these cilia emanate from the mother centriole, prior to centrosome duplication. In addition, the study of telomeric TFR2 suggests that these cilia are not directly related to the bouquet conformation during early male mouse meiosis. Instead, based on TEX14 labeling of intercellular bridges in spermatocyte cysts, we suggest that mouse meiotic cilia may have sensory roles affecting cyst function during prophase I.

cell biology↗

bioRxiv2021

Haspin participates in Aurora phosphorylation at centromeres and contributes to chromosome congression in male mouse meiosis

Chromosome segregation requires that centromeres properly attach to spindle microtubules. This is an essential step towards the accuracy of cell division and therefore must be precisely regulated in both mitosis and meiosis. One of the main centromeric regulatory signaling pathways is the Haspin-H3T3ph-chromosomal passenger complex (CPC) cascade, which is responsible for the recruitment of the CPC to the centromeres. In mitosis, Haspin kinase phosphorylates H3 at threonine 3 (H3T3ph), the essential histone mark that recruits the CPC whose catalytic component is Aurora B kinase. To date, no data has yet been presented about the action of the centromeric Haspin-H3T3ph-CPC pathway in mammalian male meiosis. We have analyzed the consequences of Haspin chemical inhibition in cultured spermatocytes using LDN-192960. Our in vitro studies suggest that Haspin kinase activity is required for proper chromosome congression during both meiotic divisions and for the recruitment of phosphorylated Aurora B at meiotic centromeres. These results have been confirmed by the characterization of the meiotic phenotype of the genetic mouse model Haspin-/-, which displays similar defects. In addition, our work demonstrates that the absence of H3T3ph histone mark does not alter SGO2 localization to meiotic centromeres. These results add new and relevant information regarding the regulation of centromere function during meiosis.

cell biology↗

bioRxiv2021

Translating outcomes from the clinical setting to preclinical models: chronic pain and functionality in chronic musculoskeletal pain

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), tenderness, and fatigue, which interferes with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for pain and muscle function in a preclinical model of CWP. We assessed correlations between pain behaviors and muscle function in a preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between outcomes existed in both settings, for usability of clinical assays in model systems. For preclinical measures, the acidic saline model of FM which induces widespread muscle pain, was used in adult female mice. Two gastrocnemius injections of acidic or physiological pH saline were given following baseline measures, five days apart. An array of adapted pain measures and functional assays were assessed for three weeks. For clinical measures, pain and functional assays were assessed in adult women with FM. For both preclinical and clinical outcomes, movement-evoked pain (MEP) was associated with mechanical pain sensitivity. Mechanical sensitivity was correlated to shifts in weight-bearing preclinically and was predictive of functionality in patients. Preclinically, it is imperative to expand how the field assesses pain behaviors when studying multi- symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models. SummaryPreclinical assessments of chronic musculoskeletal pain recapitulate several outcome measures for clinical assessment of patients with FM, particularly prolonged resting pain, and MEP.

neuroscience↗

bioRxiv2021

Multi-elemental isotope and analog tracer application to measure nutrient uptake and distribution in Malus domestica Borkh.

Plant nutrient uptake is critical to maintain an optimum balance between vegetative and reproductive growth and fruit quality. Nutrient imbalances, and more specifically the relationship of potassium, magnesium and nitrogen to calcium, can be critical for fruit quality in apple (Malus x domestica Borkh.). In perennial plants, it is difficult to conduct short-term experiments to measure plant uptake and distribution in response to either cultivar or treatment because of substantial preexisting nutrient pools already present. The use of isotopically labeled nitrogen, and nutrient analogs such as strontium and rubidium allow for the quantification of uptake and distribution that is often not possible with bulk mineral analysis. Here, the objective was to understand how scion genotype influences nutrient uptake and partitioning between aboveground and below ground parts of the tree. In this experiment, 10 atom% 15N, Strontium (Sr), and Rubidium (Rb) were applied to three different potted apple cultivars that were either treated with ABA 250 mg/L or 500 mg/L or an untreated control. After 70 days of growth, overall recovery rates of each tracer reflected the mobility of their nutrient analog. Strontium had an average tracer recovery rate of 3.9%, followed by 15N with 14.6% recovery and finally Rb with 15.1%. Independent of treatment, Gala significantly absorbed more tracer followed by Granny Smith and Honeycrisp for Rb and Sr but not 15N. These results have implications in understanding the association between aboveground factors like transpiration and nutrient uptake and distribution in apple.

plant biology↗

bioRxiv2021

Meclizine and metabotropic glutamate receptor agonists attenuate severe pain and primary sensory neuron Ca2+ activity in chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) affects about 68% of patients undergoing chemotherapy and causes severe neuropathic pain which is debilitating health problem and greatly reduces quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing. Meclizine is an H1 histamine receptor antagonist which is known to have neuroprotective effects including anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN to test agonists of mGluR8 and group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests and in vivo entire DRG neurons Ca2+ imaging using genetically-encoded Ca2+ indicator, Pirt-GCaMP3 to monitor different drug interventions on a populational ensemble level. CIPN induced increased spontaneous Ca2+ activity in DRG neurons, increased Ca2+ transient amplitudes, and hyperresponses to mechanical, thermal, and chemical stimuli. We found mGluR8 agonist, DCPG, group II mGluR agonist, LY379268, and Histamine1 receptor antagonist, meclizine all significantly attenuated mechanical and thermal pain caused by CIPN. LY379268 and meclizine, but not DCPG, attenuated DRG neuronal Ca2+ activity elevated by CIPN. Furthermore, meclizine attenuated cisplatin-induced weight loss. These results suggest group II mGluR agonist, mGluR8 agonist, and meclizine are excellent candidates to study for mechanisms and new treatment option for CIPN.

neuroscience↗

bioRxiv2021

Capsaicin pretreatment alleviates postoperative pain and reduces primary sensory neuron Ca2+ activity

After surgeries, especially thoracotomy incision, patients develop unbearable pain. Opioids are used for reducing pain but often cause serious side effects. Previously, we found that capsaicin pretreatment of the incision area alleviated spontaneous and thermal pain in a postoperative pain animal model. In the present study, we aimed to monitor primary sensory neuron Ca2+ activity in in vivo dorsal root ganglia (DRG) in a postoperative pain model using Pirt-GCaMP3 treated with capsaicin or controls. Intraplantar injection of capsaicin (0.05%) alleviated spontaneous, mechanical, and thermal postoperative pain. The Ca2+ response in in vivo DRG and in in situ spinal cord was significantly enhanced in the ipsilateral side compared to contralateral side or naive control. Primary sensory nerve fiber length was significantly decreased in the incision skin area in capsaicin-pretreated animals detected by immunohistochemistry and placental alkaline phosphatase (PLAP) staining. Thus, capsaicin pretreatment alleviates postoperative pain by suppressing Ca2+ response due to degeneration of primary sensory nerve fibers in the skin.

neuroscience↗

bioRxiv2021

Mast cell-specific receptor/corticotropin-releasing factor axis regulates alcohol withdrawal-associated headache

Rehabilitation from alcohol addiction or abuse is challenging due to alcohol withdrawal symptoms. Headache is a severe alcohol withdrawal symptom that frequently contributes to rehabilitation failure. Despite the need for treating alcohol withdrawal-induced headache, there is no appropriate therapeutic option available. Development of improved therapeutics will depend on obtaining a clearer understanding of alcohol withdrawal-induced headache pain mechanisms. Here, we show that the mast cell-specific receptor MrgprB2 controls development of alcohol withdrawal-induced headache. Withdrawing alcohol from alcohol-acclimated mice induces strong headache behaviors, including facial allodynia, facial pain expressions, and reduced walking movement, symptoms often observed in humans suffering from headache. Observed pain behaviors were abolished in MrgprB2-deficient mice. We observed in vivo spontaneous activation and hypersensitization of trigeminal ganglia neurons in alcohol withdrawal mice, but not in MrgprB2-deficient mice. Corticotropin-releasing factor (CRF) was increased in dura mater after alcohol withdrawal. Injection of CRF into dura mater resulted in activation of trigeminal ganglia neurons and vasodilation, which was accompanied by headache behavior. In cells, CRF evoked Ca2+ transients via MrgprB2 or human MrgprX2. The results indicate that alcohol withdrawal causes headache via mast cell degranulation in dura mater. The process is under control of MrgprB2/MrgprX2, which would appear to represent a potential target for treating alcohol withdrawal-related headache.

neuroscience↗

bioRxiv2021

Imaging sensory transmission and neuronal plasticity in primary sensory neurons with genetically-encoded voltage indicators

Detection of somatosensory inputs requires conversion of external stimuli into electrical signals by activation of primary sensory neurons. The mechanisms by which heterogeneous primary sensory neurons encode different somatosensory inputs remains unclear. In vivo dorsal root ganglia (DRG) imaging using genetically-encoded Ca2+ indicators (GECIs) is currently the best technique for this purpose by providing an unprecedented spatial and populational resolution. It permits the simultaneous imaging of >1800 neurons/DRG in live mice. However, this approach is not ideal given that Ca2+ is a second messenger and has inherently slow response kinetics. In contrast, genetically-encoded voltage indicators (GEVIs) have the potential to track voltage changes in multiple neurons in real time but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a novel GEVI, to dissect the temporal dynamics of noxious and non-noxious neuronal signals during mechanical, thermal, or chemical stimulation in DRG of live mice. ASAP4.4-Kv is sufficiently bright and fast enough to optically characterize individual neuron coding dynamics. Notably, using ASAP4.4-Kv, we uncovered cell-to-cell electrical synchronization between adjacent DRG neurons and robust dynamic transformations in sensory coding following tissue injury. Finally, we found that a combination of GEVI and GECI imaging empowered in vivo optical studies of sensory signal processing and integration mechanisms with optimal spatiotemporal analysis. HighlightsO_LIIn vivo ultra fast and sensitive dynamic voltage imaging of peripheral primary sensory neurons by a newly generated genetically-encoded voltage indicator. C_LIO_LIIdentification of mechanical, thermal, or chemical stimuli-evoked voltage signals with superior temporal resolution. C_LIO_LISingle-cell detection of changes in sub- and suprathreshold voltage dynamics across different disease conditions. C_LIO_LICombination of voltage (by ASAP4.4-Kv) and Ca2+ (by Pirt-GCaMP3) signals to facilitate the understanding of signal processing and integration of primary sensory neurons, especially for noxious versus non-noxious sensation. C_LI

neuroscience↗

bioRxiv2021

Anti-stress effects of the glucagon-like peptide-1 receptor agonist liraglutide in zebrafish

Stress-related disorders are extremely harmful and cause significant impacts on the individual and society. Despite the limited evidence regarding glucagon-like peptide-1 receptor (GLP-1R) and mental disorders, a few clinical and preclinical studies suggest that modulating this system could improve symptoms of stress-related disorders. This study aimed to investigate the effects of liraglutide, a GLP-1R agonist, on neurobehavioral phenotypes and brain oxidative status in adult zebrafish. Acute liraglutide promoted anxiolytic-like effects in the light/dark test, while chronic treatment blocked the impact of unpredictable chronic stress on behavioral and physiological parameters. Taken together, our study demonstrates that liraglutide is active on zebrafish brain and may counteract some of the effects induced by stress. More studies are warranted to further elucidate the potential of GLP-1R agonists for the management of brain disorders.

pharmacology and toxicology↗