Autonomic Neuroscience-Basic & Clinical最新文献

{"title":"Sex differences in heart rate and heart rate variability responses to transcutaneous auricular vagal nerve stimulation in rats.","authors":"Margherita Barbetti, Cristina Ottaviani, Julian F Thayer, Andrea Sgoifo, Luca Carnevali","doi":"10.1016/j.autneu.2024.103237","DOIUrl":"10.1016/j.autneu.2024.103237","url":null,"abstract":"<p><p>The identification of reliable biomarkers of transcutaneous auricular vagus nerve stimulation (taVNS) responsiveness is a key challenge both at the clinical and preclinical level. Vagally-mediated heart rate variability (vmHRV), a surrogate measure of cardiac vagal efferent activity, is an ideal candidate. Yet, the effects of taVNS on vmHRV remain inconclusive, likely due to the high degree of heterogeneity in stimulation protocols (e.g., taVNS parameters and side of the ear target), and little consideration of contributing factors such as sex differences. This study investigates sex differences in heart rate and vmHRV responses to different protocols of taVNS in adult rats. Male and female wild-type Groningen rats received sham or active stimulation (6 Hz or 20 Hz, 1 ms, 6 V) on the left or right auricular concha region. ECG signals were recorded before (10 min), during (20 min) and after (10 min) each session in a between-subject design. We found differential side-, frequency- and sex-specific chronotropic responses to taVNS, whereby heart rate decreased and vmHRV indexes increased at 6 Hz in males and at 20 Hz in females. Also, increases in vmHRV were only observed for right-side taVNS. The current findings suggest that biological sex should be considered for fine-tuning regulation of taVNS-induced cardiac responses and provide information regarding the side-specific effects of taVNS on vmHRV. These results will likely guide future rodent research to the choice of the most appropriate stimulation protocol in both sexes for generating information that can be translated into taVNS-related strategies in humans.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"257 ","pages":"103237"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A subset of neurons in the paraventricular nucleus of the hypothalamus directly project to liver-related premotor neurons in the ventrolateral medulla.","authors":"Lucie D Desmoulins, Adrien J R Molinas, Courtney M Dugas, Gabrielle L Williams, Sophie Kamenetsky, Roslyn K Davis, Andrei V Derbenev, Andrea Zsombok","doi":"10.1016/j.autneu.2024.103222","DOIUrl":"10.1016/j.autneu.2024.103222","url":null,"abstract":"<p><p>Sympathetic circuits including pre-sympathetic neurons in the ventrolateral medulla (VLM) and in the paraventricular nucleus (PVN) of the hypothalamus play an important role in the regulation of hepatic glucose metabolism. Despite the importance of central regulatory pathways, specific information regarding the circuits of liver-related neurons is limited. Here, we tested the hypothesis that PVN neurons are directly connected to spinally-projecting liver-related neurons in the VLM of mice. Pseudorabies virus (PRV) was used to identify liver-related neurons and time-dependent analyses revealed the location and distribution of neurons in the PVN and ventral brainstem. Four days following PRV injection, most liver-related neurons were found in the VLM and consist of both catecholaminergic (CA) and non-CA neurons. Furthermore, in addition to PRV inoculation, a monosynaptic viral tracer was used to identify VLM-projecting PVN neurons to specifically dissect PVN-VLM connections within the liver pathway. Five days following PRV inoculation, our anatomical findings revealed that a small population of liver-related PVN neurons projected to the VLM. In addition, photo-stimulation of axonal projections from SIM1-expressing PVN neurons resulted in evoked excitatory postsynaptic currents in a subset of spinally projecting liver-related neurons in the VLM. In summary, our data demonstrate the existence of monosynaptic, glutamatergic connections between PVN neurons and pre-sympathetic liver-related neurons in the VLM. These new findings regarding the central circuits involved in the sympathetic regulation of the liver provide further information necessary for developing new strategies to improve glucose homeostasis via modulation of the autonomic nerves.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"257 ","pages":"103222"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paroxysmal sympathetic hyperactivity: A common consequence of traumatic brain injury.","authors":"Fnu Nancy, Aliza Khowaja, Preet Khowaja","doi":"10.1016/j.autneu.2024.103238","DOIUrl":"10.1016/j.autneu.2024.103238","url":null,"abstract":"<p><p>Paroxysmal Sympathetic Hyperactivity (PSH) is a challenging and often underrecognized syndrome, commonly arising after a traumatic brain injury (TBI). Characterized by episodic bursts of heightened sympathetic activity, PSH presents with a distinct constellation of symptoms including hypertension, tachycardia, hyperthermia, and diaphoresis. While the exact pathophysiology remains elusive, current evidence suggests that the syndrome results from an imbalance between excitatory and inhibitory neuronal pathways within the central nervous system, leading to dysregulated autonomic responses. The unpredictable nature of PSH episodes can significantly complicate the clinical course of TBI patients, increasing the risk of secondary brain injury and other systemic complications. Management of PSH involves a combination of pharmacological agents, such as beta-blockers, opioids, and sedatives, to modulate sympathetic outflow, alongside non-pharmacological strategies aimed at minimizing environmental triggers. Early recognition and targeted intervention are crucial to improving outcomes. This communication delves into the clinical presentation, underlying mechanisms, and evolving management strategies of PSH, providing insights into its impact on the recovery of TBI patients.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"257 ","pages":"103238"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal cardiovascular control during exercise: Role of insulin resistance in the brain.","authors":"Juan A Estrada, Amane Hori, Ayumi Fukazawa, Rie Ishizawa, Norio Hotta, Han-Kyul Kim, Scott A Smith, Masaki Mizuno","doi":"10.1016/j.autneu.2025.103239","DOIUrl":"https://doi.org/10.1016/j.autneu.2025.103239","url":null,"abstract":"<p><p>During exercise circulatory adjustments to meet oxygen demands are mediated by multiple autonomic mechanisms, the skeletal muscle exercise pressor reflex (EPR), the baroreflex (BR), and by feedforward signals from central command neurons in higher brain centers. Insulin resistance in peripheral tissues includes sensitization of skeletal muscle afferents by hyperinsulinemia which is in part responsible for the abnormally heightened EPR function observed in diabetic animal models and patients. However, the role of insulin signaling within the central nervous system (CNS) is receiving increased attention as a potential therapeutic intervention in diseases with underlying insulin resistance. This review will highlight recent advances in our understanding of how insulin resistance induces changes in central signaling. The alterations in central insulin signaling produce aberrant cardiovascular responses to exercise. In particular, we will discuss the role of insulin signaling within the medullary cardiovascular control nuclei. The nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM) are key nuclei where insulin has been demonstrated to modulate cardiovascular reflexes. The first locus of integration for the EPR, BR and central command is the NTS which is high in neurons expressing insulin receptors (IRs). The IRs on these neurons are well positioned to modulate cardiovascular responses to exercise. Additionally, the differences in IR density and presence of receptor isoforms enable specificity and diversity of insulin actions within the CNS. Therefore, non-invasive delivery of insulin into the CNS may be an effective means of normalizing cardiovascular responses to exercise in patients with insulin resistance.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"258 ","pages":"103239"},"PeriodicalIF":3.2,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1, but not ATP, is required for mechanotransduction by bladder mucosal afferents in cystitis.","authors":"Wai Ping Yew, Timothy Hibberd, Nick J Spencer, Vladimir Zagorodnyuk","doi":"10.1016/j.autneu.2024.103231","DOIUrl":"10.1016/j.autneu.2024.103231","url":null,"abstract":"<p><p>Piezo ion channels play a role in bladder sensation, but the sensory afferent subtypes that utilise Piezo channels have not been fully explored. We made single-unit extracellular recordings from mucosal-projecting bladder afferents in guinea pigs with protamine/zymosan-induced cystitis. The Piezo1 agonist, Yoda1, significantly potentiated mechanosensitivity, while its antagonist, Dooku1, abolished this potentiation. The P2 purinoceptor antagonist, PPADS abolished α,β-methylene ATP-induced excitation of mucosal afferents without affecting their mechanical activation or potentiation of mechanosensitivity by Yoda1. The findings suggest Piezo1, but not ATP, is required for mechanotransduction in bladder mucosal afferents in cystitis.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":" ","pages":"103231"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-occurrence of Loeys-Dietz syndrome with postural orthostatic tachycardia syndrome: A case series","authors":"Michel Boustany ,&nbsp;Ali Arvantaj ,&nbsp;Kamal R. Chémali","doi":"10.1016/j.autneu.2024.103220","DOIUrl":"10.1016/j.autneu.2024.103220","url":null,"abstract":"<div><div>Loeys-Dietz syndrome (LDS) is a connective tissue disorder arising from mutations in the TGF- β signaling pathway. The spectrum of clinical manifestations is broad, and includes vascular, skeletal, and craniofacial abnormalities, along with joint hypermobility. No evidence of postural orthostatic tachycardia syndrome (POTS) in these patients has been reported. We report here a case series of patients with LDS presenting to the autonomic clinic and found to have POTS. Understanding the exact pathophysiology of this association requires further studies. Acknowledging the co-occurrence of these conditions is important to improve outcomes, and managing POTS in LDS patients necessitates an interdisciplinary approach.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"Article 103220"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour","authors":"Luiz Fernando Veríssimo ,&nbsp;Fernando Henrique Ferrari Alves ,&nbsp;Viviane Batista Estrada ,&nbsp;Leonardo Andre da Costa Marques ,&nbsp;Karoliny Coelho Andrade ,&nbsp;Amanda Monteiro Bonancea ,&nbsp;Natália Tavares Okano ,&nbsp;Fernando Morgan de Aguiar Corrêa ,&nbsp;Gislaine Garcia Pelosi","doi":"10.1016/j.autneu.2024.103223","DOIUrl":"10.1016/j.autneu.2024.103223","url":null,"abstract":"<div><div>Depression and cardiovascular diseases are two of the world's major health problems. Escitalopram (ESC) is widely used because of its safety in relation to other drugs in that class; however, it can affect the cardiovascular system. The present study evaluated the cardiovascular parameters of depressive-like male rats and the cardiovascular effects of ESC treatment on that condition. The EMS protocol consisted of separating the litter from the dam for 3 h over 13 days. Animals were anesthetized with tribromoethanol (250 mg/kg, intraperitoneally) and the catheters were inserted into the femoral and into the femoral vein. Depressive-like rats showed an increase in the pressor response to phenylephrine (E_max:depressive = 50.36 ± 2.997 mmHg; non-depressive = 39.51 ± 3.328 mmHg; <em>p</em> &lt; 0.05) and a reduction in the EC₅₀ (depressive = 0.6203 ± 0.03005 μg/kg; non-depressive = 0.7320 ± 0.03519 μg/kg; p &lt; 0.05) with no change in the other cardiovascular parameters. After treatment with ESC, a reduction of intrinsic heart rate was observed in the depressive-like rats (control: 342 ± 6 bpm; ESC: 316 ± 5 bpm; <em>p</em> &lt; 0.05). In addition, ESC treatment increased the bradycardic (control: −97.81 ± 8.3 bpm; ESC: −137.1 ± 12.31 bpm; <em>p</em> = 0.0236; <em>t</em> = 2.502) during the baroreflex response, caused by an increase in cardiac parasympathetic modulation in the heart, in depressive-like rats (<em>p</em> &lt; 0.001). The findings suggest that depressive-like rats showed cardiovascular changes, and that ESC treatment was able to reverse these changes, suggesting that ESC has a good safety profile for depressive patients with cardiovascular disease due to increased parasympathetic modulation.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"Article 103223"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic targets in the Postural Orthostatic Tachycardia Syndrome: A short thematic review.","authors":"Alaina C Glasgow, Joon Young Kim","doi":"10.1016/j.autneu.2024.103232","DOIUrl":"10.1016/j.autneu.2024.103232","url":null,"abstract":"<p><p>Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic autonomic condition hallmarked by orthostatic intolerance and tachycardia in the upright position. POTS impacts approximately 1-3 million people in the U.S. alone, in which the majority of patients are premenopausal women. The etiology of POTS is multi-factorial with three primary clinical subtypes, including neuropathic, hyperadrenergic, and hypovolemic POTS. Recent evidence suggests potential metabolic associations with POTS pathophysiology, particularly involving insulin resistance and abnormal vasoactive gut hormones. This review aims to characterize POTS phenotypes and explore potential metabolic links, focusing on insulin resistance and vasoactive gut hormones. Understanding the metabolic aspects of POTS pathophysiology could provide novel insights into its mechanisms and guide therapeutic approaches.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"103232"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and morphology of CGRP-IR axons in flat-mounts of whole male and female mouse atria.","authors":"Kohlton Bendowski, Yuanyuan Zhang, Ariege Bizanti, Duyen Nguyen, Adhithyaa Nair, Jichao Ma, Jin Chen, Zixi Jack Cheng","doi":"10.1016/j.autneu.2024.103221","DOIUrl":"https://doi.org/10.1016/j.autneu.2024.103221","url":null,"abstract":"<p><p>Due to a lack of anatomical studies utilizing female specimens, it is unclear how the nociceptive innervation of the mouse heart compares between sexes. To address this, flat-mount preparations of the left and right atria of male and female mice were immunohistochemically labeled for calcitonin gene-related peptide (CGRP, a common marker for nociceptive nerves), imaged, and digitally traced in high quality. The results show that 1) A network of CGRP-IR axons densely innervated the right and left atria. Large nerve bundle entry points and regional concentration of CGRP-IR axons were similar in both sexes. 2) The detailed distribution of CGRP-IR bundles and axons were digitized and mapped using Arivis (Zeiss) Vision4D software. The general distribution patterns in male and female mice were comparable to one another. 3) The density of CGRP-IR axons in the sinoatrial (SA) node region (Male: 0.0258 μm/μm² ± 0.003; Female: 0.0347 μm/μm² ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm² ± 0.001; Female: 0.0228 μm/μm² ± 0.005) were not found to be significantly different. 4) The distance between adjacent varicosities in the auricle (Male: 4.049 μm ± 0.3; Female: 4.241 μm ± 0.34), SA node region (Male: 2.812 μm ± 0.21; Female: 3.352 μm ± 0.29), and AV node region (Male: 2.999 μm ± 0.3; Female: 3.526 μm ± 0.26) were not significantly different between sexes. 5) Likewise, maximum varicosity diameters in the auricle (Male: 0.5356 μm ± 0.04; Female: 0.5274 μm ± 0.03), SA node region (Male: 0.4714 μm ± 0.02; Female: 0.5634 μm ± 0.04), and AV node region (Male: 0.5103 μm ± 0.02; Female: 0.5103 μm ± 0.03) between male and female specimens were similar. Our data shows the comparable nature of the CGRP-IR axons in mouse atria in both sexes. Moreover, this is the first time we employed flat-mount preparations of whole atria to analyze the distribution of CGRP-IR axons in male and female mice.</p>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"258 ","pages":"103221"},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baroreflex activation therapy through electrical carotid sinus stimulation","authors":"Jens Jordan ,&nbsp;Jens Tank ,&nbsp;Karsten Heusser ,&nbsp;Hannes Reuter","doi":"10.1016/j.autneu.2024.103219","DOIUrl":"10.1016/j.autneu.2024.103219","url":null,"abstract":"<div><div>An imbalance between cardiovascular parasympathetic and sympathetic activity towards sympathetic predominance has been implicated in the pathogenesis of treatment-resistant arterial hypertension and heart failure. Arterial baroreceptors control efferent cardiovascular autonomic activity and have, therefore, been recognized as potential treatment targets. Baroreflex activation therapy through electrical carotid sinus stimulation is a device-based approach to modulate cardiovascular autonomic activity. Electrical carotid sinus stimulation lowered blood pressure in various hypertensive animal models and improved cardiac remodeling and survival in preclinical models of heart failure. In human mechanistic profiling studies, electrical carotid sinus stimulation lowered blood pressure through sympathetic inhibition with substantial inter-individual variability. The first-generation device reduced blood pressure in controlled and uncontrolled clinical trials. Controlled clinical trials proving efficacy in blood pressure reduction in patients with hypertension do not exist for the currently available second-generation carotid sinus stimulator. Investigations in heart failure patients showed improved symptoms, quality of life, and natriuretic peptide biomarkers. Electrical carotid sinus stimulation is an interesting technology to modulate cardiovascular autonomic control. However, controlled trials with hard clinical endpoints are required.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"256 ","pages":"Article 103219"},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}