Stimulation of TRPV1+ sensory nerves at nape induces significant alterations in gene expression in the spleen
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE264378 | GEO | 2025/01/18
REPOSITORIES: GEO
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Project description:Stimulation of TRPV1+ sensory nerves at nape induces significant alterations in gene expression in the spleen
| PRJNA1102294 | ENA
Project description:Given the inaccessibility of human sensory neurons (SNs), it is yet to be established whether the signalling pathway between histamine 1 receptor (H1R) and transient receptor potential cation channel subfamily V member 1 (TRPV1) is conserved between humans and mammalian models. Accessible human SNs are vital for identifying TRPV1 antagonists with higher potential for success in clinical trials targeting histaminergic itch, especially given TRPV1's species specificity concerns. Hence to build a humanized histamine-dependent itch model, we derived peripheral sensory neurons from human pluripotent stem cells (hiPSC-SNs) and validated channel functionality using immunostaining, calcium imaging and multielectrode array (MEA) recordings. Here, we demonstrated that a subset of hiPSC-SNs exhibits co-expression of H1R and TRPV1, responding to both histamine and capsaicin agonists. We found that inhibiting TRPV1 prevented histamine activation. Moreover, we show that silencing histamine-sensitive neurons reduces capsaicin response, and silencing capsaicin-sensitive neurons diminishes histamine response. To assess the ability of hiPSC-SNs in TRPV1 antagonist drug screening, we evaluated two well-established hyperthermic and three thermal-neutral TRPV1 antagonists. Our finding identifies SB366791, a thermal-neutral antagonist, as a potent inhibitor of H1R activation. The use of hiPSC-SNs may therefore provide a physiologically relevant means to perform large-scale screening to discover anti-pruritic agents predictive of actual efficacy in human clinical trials.
2024-02-27 | GSE256435 | GEO
Project description:In mammals, capsaicin activates the transient receptor potential vanilloid 1 (TRPV1) channel to induce pungency, but its effects in species lacking TRPV1 remain unclear. In Drosophila melanogaster, which has no TRPV1 ortholog, capsaicin triggers proboscis reflexes, drives attraction, and shapes feeding and locomotion in a sex- specific manner. Females exhibit delayed habituation and increased sleep fragmentation, whereas both sexes reduce evening locomotion. Single-nucleus RNA sequencing (snRNA-seq) revealed broader transcriptional responses in females, including modulation of peptidergic neurons and circadian-linked glial clusters. Cell–cell communication analyses identified a female-biased TGF-β and AstA signaling axis in learning and memory centers, contrasting with male-enriched WNT, NPF, and Dh31 pathways. These results uncover TRPV1-independent mechanisms through which capsaicin influences neural circuits, highlighting sex-specific strategies for integrating sensory cues and providing a framework to explore the ecological and evolutionary significance of capsaicin sensitivity beyond nociception.
2025-09-26 | GSE305959 | GEO
Project description:Excessive inflammation causes a wide range of diseases. Here, we found that stimulating TRPV1+ nerves at the nape activated the nucleus of the solitary tract and C1 neurons in the brainstem via the somatosensory afferent pathway, and rapidly induced the secretion of corticosterone, and drove the vagal-adrenal axis to release serum catecholamines, and activated the autonomic-splenic reflex to suppress cytokine production. RNA sequencing (RNA-seq) analysis revealed that stimulating TRPV1+ nerves significantly changed the expression of genes enriched in multiple pathways related to the inflammatory response in the spleen under pathological and normal physiological conditions. TRPV1 agonist lost these anti-inflammatory effects in trpv1ko mice. Our study revealed a neural circuit that stimulating TRPV1+ somatosensory afferents at the nape could concurrently drive the sympathetic and parasympathetic efferents to synergistically induce anti-inflammatory effects. Furthermore, stimulation of TRPV1+ peripheral sensory afferents in specific body regions is an efficient therapeutic approach to treat inflammatory diseases.
| S-EPMC11834129 | biostudies-literature
Project description:Comparing the expression profiles of the genes in response to 17b-estradiol (E2) and capsaicinoids (capsaicin (CAP), dihydrocapsaicin (DHCAP), nordihydrocapsaicin (NDHCAP), nonivamide (NV))
2017-06-13 | GSE64155 | GEO
Project description:High-count microelectrode arrays implanted in peripheral nerves could restore motor function after spinal cord injury or sensory function after limb loss. In this study, we implanted Utah Slanted Electrode Arrays (USEAs) intrafascicularly at the elbow or shoulder in arm nerves of rhesus monkeys (n = 4) under isoflurane anesthesia. Input-output curves indicated that pulse-width-modulated single-electrode stimulation in each arm nerve could recruit single muscles with little or no recruitment of other muscles. Stimulus trains evoked specific, natural, hand movements, which could be combined via multielectrode stimulation to elicit coordinated power or pinch grasp. Stimulation also elicited short-latency evoked potentials (EPs) in primary somatosensory cortex, which might be used to provide sensory feedback from a prosthetic limb. These results demonstrate a high-resolution, high-channel-count interface to the peripheral nervous system for restoring hand function after neural injury or disruption or for examining nerve structure.
| S-EPMC3545468 | biostudies-literature
Project description:BackgroundWe investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke.MethodsParticipants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (stimulation intensity as the minimum intensity at which the participants reported paresthesia; five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min). Sham stimulations occurred as follows: Sham rTMS, coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure.ResultsForty participants with stroke ischemic (n = 38) and hemorrhagic (n = 2), men (n = 19) and women (n = 21), in the subacute stage (10.6 ± 6 weeks) had a mean age of 62.2 ± 9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS.ConclusionThe combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke.Clinical trial registration[clinicaltrials.gov], identifier [NCT03329807].
| S-EPMC9036089 | biostudies-literature
Project description:Capsaicin-sensitive (Trpv1-positive) sensory C-fibers derived from vagal ganglia innervate the visceral organs, and respond to inflammatory mediators and noxious stimuli. These neurons play an important role in maintenance of visceral homeostasis, and contribute to the symptoms of visceral inflammatory diseases. Vagal sensory neurons are located in two ganglia, the jugular ganglia (derived from the neural crest), and the nodose ganglia (from the epibranchial placodes). The functional difference, especially in response to immune mediators, between jugular and nodose neurons is not fully understood. In this study, we microscopically isolated murine nodose and jugular capsaicin-sensitive / Trpv1-expressing C-fiber neurons and performed transcriptome profiling using ultra-low input RNA sequencing.
2017-10-01 | GSE102123 | GEO
Project description:Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells (EECs) in response to nutrient ingestion and lower blood glucose levels by stimulation of insulin secretion and thus are defined as incretins. GLP-1 receptor (GLP-1R) expression has been identified on enteric neurons that include intrinsic afferent neurons, extrinsic spinal, and vagal sensory afferents but has not been shown to have an incretin effect through these nerves. GLP-1 and GIP enter the mesenteric lymphatic fluid (MLF) after a meal via the interstitial fluid (IF) from local tissue secretion and/or blood capillaries. We tested if MLF could induce diet-dependent intransient increases in intracellular calcium ([Ca2+]i) in cultured sensory neurons. Postprandial rat MLF, collected from the superior mesenteric lymphatic duct, induced a significant twofold higher intransient increase in [Ca2+]i in primary-cultured sensory neurons than MLF from fasted rats. Inhibition of transient receptor potential vanilloid 1 (TRPV1) and TRPV1 and ankyrin 1 cation channels (TRPA1) with ruthenium red eliminated the difference. Substance P (SP) (a peptide that stimulates insulin secretion) sensor cells cocultured with sensory neurons showed both the GLP-1R agonist exendin-4 (Ex-4) and GIP induced transient increases in [Ca2+]i directly coupled to SP secretion in the sensory nerves. Ex-4-induced release of SP required expression of either TRPA1 or TRPV1. These data identify unrecognized actions of GLP-1 and GIP as incretins by acting as neurolymphocrines and suggest a mechanism for sensory nerves to respond to the postprandial state through MLF.NEW & NOTEWORTHY Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted upon eating to lower blood sugar. GLP-1 and GIP were found to induce the secretion of substance P (SP) from cultured sensory nerves. SP enhances insulin secretion. Mesenteric lymphatic fluid (MLF) also stimulates sensory neurons in a diet-dependent manner. These studies identify new actions of GLP-1 and GIP as incretins and suggest a mechanism for sensory nerves to respond to diet through MLF.
| S-EPMC7468754 | biostudies-literature
Project description:TRPV1-Independent and Sex-Specific Capsaicin Signatures in Drosophila
| PRJNA1308527 | ENA