Autonomic Neuroscience[JOURNAL]
Sun
200 papers
Diencephalic and brainstem circuit mechanisms underlying autonomic cardiovascular adjustments to exercise: Recent insights from rodent studies.
Koba S, Narai E
Auton Neurosci · 2025 Apr · PMID 39955934 · Publisher ↗
Autonomic cardiovascular adjustments to exercise, essential for meeting the increased metabolic demands of exercising skeletal muscle, are regulated by motor volition-driven neural activation, i.e., central command. The...
Autonomic cardiovascular adjustments to exercise, essential for meeting the increased metabolic demands of exercising skeletal muscle, are regulated by motor volition-driven neural activation, i.e., central command. The contribution of brain mechanisms to these adjustments has been suggested for more than a century, yet the functional brain architecture remains incompletely understood. This article discusses recent findings primarily obtained from rodent studies utilizing advanced experimental tools, particularly those enabled by genetic engineering, such as optogenetics and viral neural tracing, to elucidate the diencephalic and brainstem circuits responsible for autonomic cardiovascular adjustments during voluntary exercise. Particular attention is paid to the central neural pathways and specific neuronal populations involved in transmitting central command signals, that drive not only somatic muscular activity but also autonomic cardiovascular responses. The uncovered diencephalic and brainstem circuits are relevant to understanding the brain substrate of central command, which is essential for maintaining cellular homeostasis and enhancing physical performance. Future studies and potential subjects for further investigation to deepen our understanding of the brain mechanisms underlying autonomic cardiovascular regulation are also discussed.
Functional knock out of Acid Sensing Ion Channel 3 prevents the exaggerated exercise pressor reflex in rats exercising on a treadmill.
Thomas GD, Higgins SP, Matthew Kuczmarski J … +4 more , Ducrocq GP, Anselmi L, Ruiz-Velasco V, Kaufman MP
Auton Neurosci · 2025 Apr · PMID 39955933 · Full text
We have compared the cardiovascular responses to treadmill exercise between wild-type (WT) Wistar Kyoto rats with their ASIC3 knock out (KO) counterparts both before and after their femoral arteries were bilaterally liga...
We have compared the cardiovascular responses to treadmill exercise between wild-type (WT) Wistar Kyoto rats with their ASIC3 knock out (KO) counterparts both before and after their femoral arteries were bilaterally ligated. The rats were instrumented with radiotelemetry devices to measure arterial blood pressure and ran at a treadmill speed of 15-20 m/min. We found no difference in the pressor and cardioaccelerator responses to exercise between the WT and the ASIC3 KO rats when their femoral arteries were freely perfused. In contrast, the WT rats, but not the ASIC3 KO rats, displayed significantly larger peak and integrated pressor responses to treadmill exercise after both femoral arteries were ligated for 3 days. We also examined the effect of bilaterally injecting APETx2 into the substance of the gastrocnemius muscles on the cardiovascular responses to treadmill exercise in both the WT and the ASIC3 KO rats. We found that APETx2, an ASIC3 antagonist, attenuated the integrated pressor responses to exercise in the WT rats, after but not before the femoral arteries were ligated. Injection of APETx2 into the gastrocnemius muscles had no effect on the responses to exercise in the ASIC3 KO rats regardless of whether their femoral arteries were freely perfused or ligated. Our findings in conscious rats exercising on a treadmill extend our previous findings in reduced preparations in which we reported that ASIC3 "receptors" presumably on the intramuscular endings of group IV afferents play an important role in evoking the exaggerated component of the exercise pressor reflex induced by ischemia.
Distribution and morphology of CGRP-IR axons in flat-mounts of whole male and female mouse atria.
Bendowski K, Zhang Y, Bizanti A … +5 more , Nguyen D, Nair A, Ma J, Chen J, Cheng ZJ
Auton Neurosci · 2025 Apr · PMID 39879734 · Full text
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 atri...
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/μm ± 0.003; Female: 0.0347 μm/μm ± 0.006) and atrioventricular (AV) node region (Male: 0.0138 μm/μm ± 0.001; Female: 0.0228 μm/μm ± 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.
Abnormal cardiovascular control during exercise: Role of insulin resistance in the brain.
Estrada JA, Hori A, Fukazawa A … +5 more , Ishizawa R, Hotta N, Kim HK, Smith SA, Mizuno M
Auton Neurosci · 2025 Apr · PMID 39874739 · Full text
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 centra...
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.
Paroxysmal sympathetic hyperactivity: A common consequence of traumatic brain injury.
Nancy F, Khowaja A, Khowaja P
Auton Neurosci · 2025 Feb · PMID 39787792 · Publisher ↗
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,...
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.
Sex differences in heart rate and heart rate variability responses to transcutaneous auricular vagal nerve stimulation in rats.
Barbetti M, Ottaviani C, Thayer JF … +2 more , Sgoifo A, Carnevali L
Auton Neurosci · 2025 Feb · PMID 39693842 · Publisher ↗
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...
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.
A subset of neurons in the paraventricular nucleus of the hypothalamus directly project to liver-related premotor neurons in the ventrolateral medulla.
Desmoulins LD, Molinas AJR, Dugas CM … +5 more , Williams GL, Kamenetsky S, Davis RK, Derbenev AV, Zsombok A
Auton Neurosci · 2025 Feb · PMID 39647176 · Full text
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 metabolis...
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.
Metabolic targets in the Postural Orthostatic Tachycardia Syndrome: A short thematic review.
Glasgow AC, Kim JY
Auton Neurosci · 2024 Dec · PMID 39631266 · Publisher ↗
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. a...
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.
Piezo1, but not ATP, is required for mechanotransduction by bladder mucosal afferents in cystitis.
Yew WP, Hibberd T, Spencer NJ … +1 more , Zagorodnyuk V
Auton Neurosci · 2024 Dec · PMID 39627069 · Publisher ↗
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 bladde...
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.
Cardiovascular effects of early maternal separation and escitalopram treatment in rats with depressive-like behaviour.
Veríssimo LF, Alves FHF, Estrada VB … +6 more , da Costa Marques LA, Andrade KC, Bonancea AM, Okano NT, Corrêa FMA, Pelosi GG
Auton Neurosci · 2024 Dec · PMID 39616948 · Publisher ↗
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 cardiovasc...
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 (Edepressive = 50.36 ± 2.997 mmHg; non-depressive = 39.51 ± 3.328 mmHg; p < 0.05) and a reduction in the EC (depressive = 0.6203 ± 0.03005 μg/kg; non-depressive = 0.7320 ± 0.03519 μg/kg; p < 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; p < 0.05). In addition, ESC treatment increased the bradycardic (control: -97.81 ± 8.3 bpm; ESC: -137.1 ± 12.31 bpm; p = 0.0236; t = 2.502) during the baroreflex response, caused by an increase in cardiac parasympathetic modulation in the heart, in depressive-like rats (p < 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.
Co-occurrence of Loeys-Dietz syndrome with postural orthostatic tachycardia syndrome: A case series.
Boustany M, Arvantaj A, Chémali KR
Auton Neurosci · 2024 Dec · PMID 39612734 · Publisher ↗
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 abnor...
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.
Intrinsic versus extrinsic contribution to intraindividual sweat rate variability of individual eccrine glands.
Woolf EK, Wells N, Moore J … +2 more , Northway S, Buono MJ
Auton Neurosci · 2024 Dec · PMID 39550987 · Full text
The purpose of the current study was twofold. First, to determine the intraindividual variability of sweat rate per gland for a given skin location during exercise in the heat. Second, to determine the relative importanc...
The purpose of the current study was twofold. First, to determine the intraindividual variability of sweat rate per gland for a given skin location during exercise in the heat. Second, to determine the relative importance of intrinsic vs. extrinsic factors as the source of the intraindividual variability in the sweat rate per gland. Sweat rate of individual eccrine glands on the forearm was measured following pilocarpine iontophoresis and during exercise in the heat. In five participants during exercise in the heat, the measured sweat rate for individual forearm eccrine glands (n = 500) ranged from 0.5 nL/gland/min to 16 nL/gland/min, or over a 30-fold difference. The mean (SD) intraindividual coefficient of variation in sweat rate per gland was 36 (5)% and 49 (10)% (p = 0.008) following pilocarpine iontophoresis and during exercise in the heat, respectively. Such results suggest that intrinsic factors (i.e., sweat gland size and cholinergic sensitivity) contribute approximately three times more than extrinsic factors (i.e., sweat gland nerve fiber density and threshold amplitude) towards explaining the large intra-person variability in sweat rate per gland seen during exercise in the heat.
Baroreflex activation therapy through electrical carotid sinus stimulation.
Jordan J, Tank J, Heusser K … +1 more , Reuter H
Auton Neurosci · 2024 Dec · PMID 39549378 · Publisher ↗
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. Arteri...
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.
The role of peripheral venous distension reflex in regulating hemodynamics: mini review.
Hamaoka T, Sinoway LI, Cui J
Auton Neurosci · 2024 Dec · PMID 39270515 · Full text
Significant volume is pooled in veins in humans and the amount is dramatically altered by various physiological stresses and diseases. Several animal and human studies demonstrated that limb venous distension evoked sign...
Significant volume is pooled in veins in humans and the amount is dramatically altered by various physiological stresses and diseases. Several animal and human studies demonstrated that limb venous distension evoked significant increases in blood pressure and sympathetic nerve activity (venous distension reflex, VDR). VDR has attracted much attention because of its potential to explain the still unknown mechanism of autonomic dysfunction in several diseases, which would lead to a new treatment approach. This mini review discusses accumulated evidence of VDR at this point and what should be investigated in the future to apply the current understanding of VDR in clinical practice.
Intrasubject reproducibility of supine norepinephrine plasma concentrations in patients with cardiovascular sympathetic failure.
Carrozzo G, Miglis MG, Contin M … +4 more , Cani I, Cortelli P, Guaraldi P, Calandra-Buonaura G
Auton Neurosci · 2024 Dec · PMID 39260098 · Publisher ↗
BACKGROUND: Plasma levels of the catecholamine norepinephrine (NE) has emerged as a useful tool to help differentiate pre- and post-ganglionic disorders in patients with cardiovascular autonomic failure (AF). However, da...
BACKGROUND: Plasma levels of the catecholamine norepinephrine (NE) has emerged as a useful tool to help differentiate pre- and post-ganglionic disorders in patients with cardiovascular autonomic failure (AF). However, data on intrasubject reliability in individuals with these conditions are limited. We evaluated the intrasubject reproducibility of supine plasma NE levels drawn across two consecutive time points under controlled conditions during head-up table testing in a large cohort of patients with alpha-synucleinopathies and both pre- and post-ganglionic cardiovascular AF. METHODS: Antecubital venous blood drawn via an indwelling cannula with the subject supine was assayed for plasma level of catecholamines. We collected two consecutive samples, the first after 20 min of supine rest (NE1) and the second 5 min later (NE2), from a group of 279 participants including 57 with Parkinson's disease/Lewy body dementia (44 M; 65.5 ± 11.1 y), 131 with multiple system atrophy (81 M; 63.2 ± 8.5 y), 41 with pure autonomic failure (25 M, 65.1 ± 9.3 y), and 50 healthy controls (27 M; 46.7 ± 19.4 y). RESULTS: We found no difference between NE1 and NE2 (p = 0.645), with a mean intrasubject reproducibility (NE maximum - NE minimum) × 100 / NE maximum) of 11.5 % ± 10.64. This finding was confirmed when controlling for diagnosis (p = 0.669), gender (p = 0.493), age (p = 0.865), disease duration (p = 0.596) or considering all factors together (p = 0.527). CONCLUSIONS: We found excellent test-retest reliability of consecutive supine NE measurements in patients with alpha-synucleinopathies and cardiovascular AF, independent of age, gender and disease duration. This lends evidence to support the use of a single supine NE measurement in these conditions.
Renal interoception in health and disease.
Evans LC, Dailey-Krempel B, Lauar MR … +3 more , Dayton A, Vulchanova L, Osborn JW
Auton Neurosci · 2024 Oct · PMID 39128142 · Full text
Catheter based renal denervation has recently been FDA approved for the treatment of hypertension. Traditionally, the anti-hypertensive effects of renal denervation have been attributed to the ablation of the efferent sy...
Catheter based renal denervation has recently been FDA approved for the treatment of hypertension. Traditionally, the anti-hypertensive effects of renal denervation have been attributed to the ablation of the efferent sympathetic renal nerves. In recent years the role of the afferent sensory renal nerves in the regulation of blood pressure has received increased attention. In addition, afferent renal denervation is associated with reductions in sympathetic nervous system activity. This suggests that reductions in sympathetic drive to organs other than the kidney may contribute to the non-renal beneficial effects observed in clinical trials of catheter based renal denervation. In this review we will provide an overview of the role of the afferent renal nerves in the regulation of renal function and the development of pathophysiologies, both renal and non-renal. We will also describe the central projections of the afferent renal nerves, to give context to the responses seen following their ablation and activation. Finally, we will discuss the emerging role of the kidney as an interoceptive organ. We will describe the potential role of the kidney in the regulation of interoceptive sensitivity and in this context, speculate on the possible pathological consequences of altered renal function.
Carotid body interoception in health and disease.
Conde SV, Martins FO, Sacramento JF
Auton Neurosci · 2024 Oct · PMID 39121687 · Publisher ↗
Interoception entails perceiving or being aware of the internal state of the body, playing a pivotal role in regulating processes such as heartbeat, digestion, glucose metabolism, and respiration. The carotid body (CB) s...
Interoception entails perceiving or being aware of the internal state of the body, playing a pivotal role in regulating processes such as heartbeat, digestion, glucose metabolism, and respiration. The carotid body (CB) serves as an interoceptive organ, transmitting information to the brain via its sensitive nerve, the carotid sinus nerve, to maintain homeostasis. While traditionally known for sensing oxygen, carbon dioxide, and pH levels, the CB is now recognized to possess additional interoceptive properties, detecting various mediators involved in blood pressure regulation, inflammation, and glucose homeostasis, among other physiological functions. Furthermore, in the last decades CB dysfunction has been linked to diseases like sleep apnea, essential hypertension, and diabetes. In this review manuscript, we make a concise overview of the traditional interoceptive functions of the CB, acting as a sensor for oxygen levels, carbon dioxide levels, and pH, and introduce the novel interoceptive properties of the CB related to vascular, glucose and energy regulation. Additionally, we revise the contribution of the CB to the onset and progression of metabolic diseases, delving into the potential dysfunction of its interoceptive metabolic functions as a contributing factor to pathophysiology. Finally, we postulate the use of therapeutic interventions targeting the metabolic interoceptive properties of the CB as a potential avenue for addressing metabolic diseases.
Optogenetic modulation of cardiac autonomic nervous system.
Hernández-Domínguez RA, Herrera-Orozco JF, Salazar-Calderón GE … +7 more , Chávez-Canales M, Márquez MF, González-Álvarez F, Totomoch-Serra A, Reyes-Cruz T, Lip F, Aceves-Buendía JJ
Auton Neurosci · 2024 Oct · PMID 39059299 · Publisher ↗
The following is a narrative review of the fundamentals of optogenetics. It focuses on the advantages and constraints of manipulating the autonomic nervous system by modifying the pathophysiological characteristics that...
The following is a narrative review of the fundamentals of optogenetics. It focuses on the advantages and constraints of manipulating the autonomic nervous system by modifying the pathophysiological characteristics that arise in different diseases. Although the use of this technique is currently experimental, we will discuss improvements that have been implemented and identify the necessary measures for potential preclinical translation in the control of the cardiac autonomic nervous system.
Research progress on pathogenesis of chronic fatigue syndrome and treatment of traditional Chinese and Western medicine.
Liu T, Sun W, Guo S … +10 more , Chen T, Zhu M, Yuan Z, Li B, Lu J, Shao Y, Qu Y, Sun Z, Feng C, Yang T
Auton Neurosci · 2024 Oct · PMID 39047501 · Publisher ↗
Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, a...
Chronic Fatigue Syndrome (CFS) is a complex and perplexing medical disorder primarily characterized by persistent and debilitating fatigue, often accompanied by a constellation of symptoms, including weakness, dyspnea, arthromyalgia, sore throat, and disrupted sleep patterns. CFS is defined by its persistent or recurrent manifestation for a minimum duration of six months, marked by an enduring and unrelenting fatigue that remains refractory to rest. In recent decades, this condition has garnered significant attention within the medical community. While the precise etiology of CFS remains elusive, it is postulated to be multifactorial. CFS is potentially associated with various contributory factors such as infections, chronic stress, genetic predisposition, immune dysregulation, and psychosocial influences. The pathophysiological underpinnings of CFS encompass viral infections, immune system dysregulation, neuroendocrine aberrations, heightened oxidative stress, and perturbations in gut microbiota. Presently, clinical management predominantly relies on pharmaceutical interventions or singular therapeutic modalities, offering alleviation of specific symptoms but exhibiting inherent limitations. Traditional Chinese Medicine (TCM) interventions have emerged as a promising paradigm, demonstrating notable efficacy through their multimodal, multi-target, multi-pathway approach, and holistic regulatory mechanisms. These interventions effectively address the lacunae in contemporary medical interventions. This comprehensive review synthesizes recent advancements in the understanding of the etiological factors, pathophysiological mechanisms, and interventional strategies for CFS, drawing from a corpus of domestic and international literature. Its aim is to furnish valuable insights for clinicians actively involved in diagnosing and treating CFS, as well as for pharmaceutical researchers delving into innovative drug development pathways. Moreover, it seeks to address the intricate challenges confronted by clinical practitioners in managing this incapacitating condition.
Population study of pupillary unrest in ambient light.
McKay RE, Kohn M, Schwartz E … +1 more , Larson MD
Auton Neurosci · 2024 Aug · PMID 38996657 · Publisher ↗
INTRODUCTION: Pupillary unrest in ambient light (PUAL) describes the fluctuation of pupil diameter observed in normal, awake subjects under typical levels of indoor light. PUAL becomes low to absent in young healthy subj...
INTRODUCTION: Pupillary unrest in ambient light (PUAL) describes the fluctuation of pupil diameter observed in normal, awake subjects under typical levels of indoor light. PUAL becomes low to absent in young healthy subjects during opioid intoxication. We sought to determine the age-related distribution of PUAL values in a random sample of ambulatory participants. METHODS: Subjects ≥18 years of age were recruited. All were identified by age range (18-29, 30-49, 50-69, and ≥70), and surveyed for diabetes, beta-blocker use, and prior 24-hour opioid use. Relationship between mean PUAL, age group, comorbidity and opioid use were examined by Kruskal Wallis test, and PUAL and was modeled using stepwise multilevel linear regression, including diabetes, beta blocker use, prior 24-hour opioid use, autonomic dysfunction, and pupil diameter as fixed effects and subject as random effect. RESULTS: Among 150 subjects, 17 reported diabetes, 12 reported beta-blocker use, 14 reported prior 24-hour opioid use, and 120 reported no comorbid conditions. PUAL declined in higher age categories (by 0.0307, P < 0.001), with diabetes (by 0.0481, P = 0.025), and with beta-blocker use (by 0.0616, P = 0.005). Opioid related PUAL decline was observed, but statistical significance varied by model. Among healthy subjects, no PUAL value fell within range indicating high likelihood of opioid toxicity based on previous data from healthy subjects undergoing opioid infusion. CONCLUSION: PUAL declined in higher age groups, diabetes and beta-blocker use, conditions associated with impaired autonomic function, and with opioid use but significance varied depending on the chosen model.
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