Autonomic Neuroscience[JOURNAL]
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200 papers
Increased adrenocortical activity in patients with vasovagal syncope.
Bačkorová B, Lazúrová Z, Lewaskiewicz P … +2 more , Mitro P, Lazúrová I
Auton Neurosci · 2024 Aug · PMID 38959624 · Publisher ↗
OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may m...
OBJECTIVE: Syncope is a transient loss of consciousness resulting from cerebral hypoperfusion. Vasovagal syncope (VVS) is a form of orthostatic intolerance (OI). Its clinical signs such as dizziness and hypotension may mimic symptoms of adrenal insufficiency. The objective of this study was to evaluate the adrenal gland function in patients with vasovagal syncope after stimulation with synthetic adrenocorticotropic hormone (ACTH). DESIGN: Case-control study on patients with VVS and healthy controls. METHODS: The study involved 42 participants, including 27 patients diagnosed with VVS using the head-up tilt test and 15 healthy individuals with no history of syncope or any orthostatic symptoms. Serum cortisol and aldosterone concentrations were measured under basal conditions and at 30 and 60 min after intramuscular ACTH stimulation. RESULTS: Patients with VVS had significantly higher cortisol levels at baseline (441 ± 143 vs. 331 ± 84.7 nmol/L, p = 0.01), at 30 min (802 ± 143 vs. 686 ± 105 nmol/L, p = 0.01) and at 60 min (931 ± 141 nmol/L vs. 793 ± 147 nmol/L, p = 0.001) after ACTH administration (Synacthen 250 μg). Plasma aldosterone increased after ACTH stimulation, but did not show significant differences among groups. Furthermore, there was also no significant correlation between cortisol levels and blood pressure or heart rate. CONCLUSION: Patients diagnosed with VVS have higher cortisol levels both at baseline and after ACTH stimulation. This finding indicates that individuals with VVS have higher adrenocortical activity potentially as a response to the orthostatic stress induced by syncope, which acts as a stressful stimulus on the autonomic nervous system.
Reduction of long COVID symptoms after stellate ganglion block: A retrospective chart review study.
Duricka D, Liu L
Auton Neurosci · 2024 Aug · PMID 38901177 · Publisher ↗
The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of sym...
The SARS-CoV-2 pandemic has left millions of individuals with a host of post-viral symptoms that can be debilitating and persist indefinitely. To date there are no definitive tests or treatments for the collection of symptoms known as "Long COVID" or Post-acute sequelae of COVID-19 (PASC). Following our initial case report detailing improvement of Long COVID symptoms after sequential bilateral stellate ganglion blockade (SGB), we performed a retrospective chart analysis study on individuals treated with the same protocol over the course of six months (2021-2022) in our clinic. Patients self-reported symptoms on a 10-point scale as part of optional patient follow-up using an online survey. After one month or more following treatment, patients reported striking reductions in Fatigue, Worsening of Symptoms following Mental and Physical Activity, Memory Problems, Problems Concentrating, Sleep Problems, Anxiety, and Depression. Loss of Taste and Loss of Smell in some individuals did not respond to treatment, likely indicating structural damage following infection. This study suggests that neuromodulation may provide relief of Long COVID symptoms for at least a subset of individuals, and provides support for prospective studies of this potential treatment.
Transcutaneous vagal nerve stimulation during lower body negative pressure.
Petersen JCG, Becker R, Petersen LG
Auton Neurosci · 2024 Aug · PMID 38896931 · Publisher ↗
BACKGROUND: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular br...
BACKGROUND: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP). METHOD: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded. RESULTS: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05). CONCLUSION: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.
Adrenergic relaxations in an in situ urinary bladder model evoked by stimulation of sensory pelvic and pudendal nerves in the rat.
Stenqvist J, Tobin G
Auton Neurosci · 2024 Aug · PMID 38875740 · Publisher ↗
Urinary bladder dysfunction might be related to disturbances at different levels of the micturition reflex arc. The current study aimed to further develop and evaluate a split bladder model for detecting and analysing re...
Urinary bladder dysfunction might be related to disturbances at different levels of the micturition reflex arc. The current study aimed to further develop and evaluate a split bladder model for detecting and analysing relaxatory signalling in the rat urinary bladder. The model allows for discrimination between effects at the efferent and the afferent side of the innervation. In in vivo experiments, the stimulation at a low frequency (1 Hz) of the ipsilateral pelvic nerve tended to evoke relaxation of the split bladder half (contralateral side; -1.0 ± 0.4 mN; n = 5), in contrast to high frequency-evoked contractions. In preparations in which the contralateral pelvic nerve was cut the relaxation occurred at a wider range of frequencies (0.5-2 Hz). In separate experiments, responses to 1 and 2 Hz were studied before and after intravenous injections of propranolol (1 mg/kg IV). The presence of propranolol significantly shifted the relaxations into contractions. Also, electrical stimulation of the ipsilateral pudendal nerve evoked relaxations of similar magnitude as for the pelvic stimulations, which were also affected by propranolol. In control in vitro experiments, substances with β-adrenoceptor agonism, in contrast to a selective α-agonist, evoked relaxations. The current study shows that the split bladder model can be used for in vivo studies of relaxations. In the model, reflex-evoked sympathetic responses caused relaxations at low intensity stimulation. The involvement of β-adrenoceptors is supported by the sensitivity to propranolol and by the in vitro observations.
Nadir blood pressure responses to longer consecutive cardiac cycle sequences absent of sympathetic bursts are associated with popliteal endothelial-dependent dilation.
O'Brien MW, Schwartz BD, Petterson JL … +3 more , Courish MK, Shivgulam ME, Kimmerly DS
Auton Neurosci · 2024 Aug · PMID 38852226 · Publisher ↗
PURPOSE: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the informatio...
PURPOSE: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP. METHODS: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined. RESULTS: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72). CONCLUSION: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA.
Acute hypernatremia increases functional connectivity of NaCl sensing regions in the human brain: An fMRI pilot study.
Stock JM, Romberger NT, McMillan RK … +5 more , Chung JW, Wenner MM, Stocker SD, Farquhar WB, Burciu RG
Auton Neurosci · 2024 Aug · PMID 38805791 · Full text
Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. Howev...
Rodent studies demonstrated specialized sodium chloride (NaCl) sensing neurons in the circumventricular organs, which mediate changes in sympathetic nerve activity, arginine vasopressin, thirst, and blood pressure. However, the neural pathways involved in NaCl sensing in the human brain are incompletely understood. The purpose of this pilot study was to determine if acute hypernatremia alters the functional connectivity of NaCl-sensing regions of the brain in healthy young adults. Resting-state fMRI scans were acquired in 13 participants at baseline and during a 30 min hypertonic saline infusion (HSI). We used a seed-based approach to analyze the data, focusing on the subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) as regions of interest (ROIs). Blood chemistry and perceived thirst were assessed pre- and post-infusion. As expected, serum sodium increased from pre- to post-infusion in the HSI group. The primary finding of this pilot study was that the functional connectivity between the SFO and a cluster within the OVLT increased from baseline to the late-phase of the HSI. Bidirectional connectivity changes were found with cortical regions, with some regions showing increased connectivity with sodium-sensing regions while others showed decreased connectivity. Furthermore, the functional connectivity between the SFO and the posterior cingulate cortex (a control ROI) did not change from baseline to the late-phase of the HSI. This finding indicates a distinct response within the NaCl sensing network in the human brain specifically related to acute hypernatremia that will need to be replicated in large-scale studies.
Neural mechanisms of respiratory interoception.
Chan PS, Lee LY, Davenport PW
Auton Neurosci · 2024 Jun · PMID 38696917 · Publisher ↗
Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediati...
Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. Dyspnea can be differentiated into specific modalities. These respiratory sensory modalities lead to a general sensation of an Urge-to-Breathe, driven by a need to compensate for the modulation of ventilation that has occurred due to factors that have affected breathing. The multiafferent system for respiratory interoception can also lead to interpretation of the sensory signals resulting in respiratory related sensory experiences, including the Urge-to-Cough and Urge-to-Swallow. These behaviors are modalities that can be driven through the differentiation and integration of multiple afferent input into the respiratory neural comparator. Respiratory sensations require neural somatic and visceral interoceptive elements that include gated attention and detection leading to respiratory modality discrimination with subsequent cognitive decision and behavioral compensation. Studies of brain areas mediating cortical and subcortical respiratory sensory pathways are summarized and used to develop a model of an integrated respiratory neural network mediating respiratory interoception.
Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort.
Beach P, McKay JL
Auton Neurosci · 2024 Jun · PMID 38692034 · Full text
BACKGROUND: Reported orthostatic hypotension (OH) prevalence in Parkinson's disease (PD) varies widely, with few studies evaluating specifically neurogenic-OH (nOH). The ratio of orthostatic heart rate (HR) to systolic b...
BACKGROUND: Reported orthostatic hypotension (OH) prevalence in Parkinson's disease (PD) varies widely, with few studies evaluating specifically neurogenic-OH (nOH). The ratio of orthostatic heart rate (HR) to systolic blood pressure (SBP) change (Δ) is a valid screening method to stratify nOH/non-nOH but has had minimal epidemiologic application. OBJECTIVE: To estimate the prevalence of nOH and non-nOH in the PPMI using the ΔHR/ΔSBP ratio and examine associations between nOH and various motor and non-motor measures. METHODS: Longitudinal orthostatic vitals and motor and non-motor measures were extracted (baseline-month 48). Patients were consensus criteria classified as OH+/-, with ΔHR/ΔSBP sub-classification to nOH (ΔHR/ΔSBP < 0.5) or non-nOH (ratio ≥ 0.5). Prevalence was determined across visits. Independent linear mixed models tested associations between nOH/non-nOH and clinical variables. RESULTS: Of N = 907 PD with baseline orthostatic vitals, 3.9 % and 1.8 % exhibited nOH and non-nOH, respectively. Prevalence of nOH/non-nOH increased yearly (P = 0.012, chi-square), though with modest magnitude (baseline: 5.6 % [95 % CI: 4.3-7.3 %]; month 48: 8.6 % [6.4-11.5 %]). nOH patients were older than PD with no OH and nOH was associated with greater impairment of motor and independent functioning than non-nOH/OH- groups. Cognitive function and typical OH symptoms were worse in PD + OH, generally. CONCLUSIONS: nOH prevalence was greater than non-nOH in the PPMI early PD cohort, with modest prevalence increase over time. Our findings are consistent with prior studies of large cohorts that evaluated nOH, specifically. Those with early PD and nOH were likelier to be older and suffer from greater motor and functional impairment, but OH presence was generally associated with more cognitive impairment.
Voluntary wheel running as a promising strategy to promote autonomic resilience to social stress in females: Vagal tone lies at the heart of the matter.
Pate BS, Smiley CE, Harrington EN … +5 more , Bielicki BH, Davis JM, Reagan LP, Grillo CA, Wood SK
Auton Neurosci · 2024 Jun · PMID 38677130 · Full text
Social stress is a major risk factor for comorbid conditions including cardiovascular disease and depression. While women exhibit 2-3× the risk for these stress-related disorders compared to men, the mechanisms underlyin...
Social stress is a major risk factor for comorbid conditions including cardiovascular disease and depression. While women exhibit 2-3× the risk for these stress-related disorders compared to men, the mechanisms underlying heightened stress susceptibility among females remain largely unknown. Due to a lack in understanding of the pathophysiology underlying stress-induced comorbidities among women, there has been a significant challenge in developing effective therapeutics. Recently, a causal role for inflammation has been established in the onset and progression of comorbid cardiovascular disease/depression, with women exhibiting increased sensitivity to stress-induced immune signaling. Importantly, reduced vagal tone is also implicated in stress susceptibility, through a reduction in the vagus nerve's well-recognized anti-inflammatory properties. Thus, examining therapeutic strategies that stabilize vagal tone during stress may shed light on novel targets for promoting stress resilience among women. Recently, accumulating evidence has demonstrated that physical activity exerts cardio- and neuro-protective effects by enhancing vagal tone. Based on this evidence, this mini review provides an overview of comorbid cardiovascular and behavioral dysfunction in females, the role of inflammation in these disorders, how stress may impart its negative effects on the vagus nerve, and how exercise may act as a preventative. Further, we highlight a critical gap in the literature with regard to the study of females in this field. This review also presents novel data that are the first to demonstrate a protective role for voluntary wheel running over vagal tone and biomarkers of cardiac dysfunction in the face of social stress exposure in female rats.
Interoceptive signals from the heart and coronary circulation in health and disease.
Moore JP
Auton Neurosci · 2024 Jun · PMID 38677129 · Publisher ↗
This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and cor...
This review considers interoceptive signalling from the heart and coronary circulation. Vagal and cardiac sympathetic afferent sensory nerve endings are distributed throughout the atria, ventricles (mainly left), and coronary artery. A small proportion of cardiac receptors attached to thick myelinated vagal afferents are tonically active during the cardiac cycle. Dependent upon location, these mechanoreceptors detect fluctuations in atrial volume and coronary arterial perfusion. Atrial volume and coronary arterial signals contribute to beat-to-beat feedback control and physiological homeostasis. Most cardiac receptors are attached to thinly myelinated or nonmyelinated C fibres, many of which are unresponsive to the cardiac cycle. Of these, there are many chemically sensitive cardiac receptors which are activated during myocardial stress by locally released endogenous substances. In contrast, some tonically inactive receptors become activated by irregular ventricular wall mechanics or by distortion of the ischaemic myocardium. Furthermore, some are excited both by chemical mediators of ischaemia and wall abnormalities. Reflex responses arising from cardiac receptors attached to thinly myelinated or nonmyelinated are complex. Impulses that project centrally through vagal afferents elicit sympathoinhibition and hypotension, whereas impulses travelling in cardiac sympathetic afferents and spinal pathways elicit sympathoexcitation and hypertension. Two opposing cardiac reflexes may provide a mechanism for fine-tuning a composite haemodynamic response during myocardial stress. Sympathetic afferents provide the primary pathway for transmission of cardiac nociception to the central nervous system. However, activation of sympathetic afferents may increase susceptibility to life-threatening arrhythmias. Notably, the cardiac sympathetic afferent reflex predominates in pathophysiological states including hypertension and heart failure.
Anticipating noxious stimulation rather than afferent nociceptive input may evoke pupil asymmetry.
Drummond PD
Auton Neurosci · 2024 Jun · PMID 38677128 · Publisher ↗
Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of this pupil asymmetry, electrical stimuli, delivere...
Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of this pupil asymmetry, electrical stimuli, delivered alone or 200 ms before or after an acoustic startle stimulus, were administered to one ankle under four experimental conditions: with or without a 1.6 s anticipatory period, or while the forearm ipsilateral or contralateral to the electrical stimulus was heated tonically to induce moderate pain (15 healthy participants in each condition). Pupil diameter was measured at the start of each trial, at stimulus delivery, and each second for 5 s after stimulus delivery. At the start of the first trial, the pupil ipsilateral to the side on which electric shocks were later delivered was larger than the contralateral pupil. Both pupils dilated robustly during the anticipatory period and dilated further during single- and dual-stimulus trials. However, pupil asymmetry persisted throughout the experiment. Tonically-applied forearm heat-pain modulated the pupillary response to phasic electrical stimuli, with a slight trend for dilatation to be greater contralateral to the forearm being heated. Together, these findings suggest that focusing anxiously on the expected site of noxious stimulation was associated with dilatation of the ipsilateral pupil whereas phasic nociceptive stimuli and psychological arousal triggered bilateral pupillary dilatation. It was concluded that preparatory cognitive activity rather than phasic afferent nociceptive input is associated with pupillary signs of lateralized activity in the locus coeruleus.
Tributyltin (TBT) toxicity: Effects on enteric neuronal plasticity and intestinal barrier of rats' duodenum.
Oliveira ICCS, Marinsek GP, Correia LVB … +3 more , da Silva RCB, Castro IB, Mari RB
Auton Neurosci · 2024 Jun · PMID 38669866 · Publisher ↗
Tributyltin (TBT) is a biocide used in the formulation of antifouling paints and it is highly harmful. Despite the ban, the compound persists in the environment, contaminating marine foodstuffs and household products. Th...
Tributyltin (TBT) is a biocide used in the formulation of antifouling paints and it is highly harmful. Despite the ban, the compound persists in the environment, contaminating marine foodstuffs and household products. Therefore, considering the route of exposure to the contaminant, the gastrointestinal tract (GIT) acts as an important barrier against harmful substances and is a potential biomarker for understanding the consequences of these agents. This work aimed to evaluate histological and neuronal alterations in the duodenum of male Wistar rats that received 20 ng/g TBT and 600 ng/g via gavage for 30 consecutive days. After the experimental period, the animals were euthanized, and the duodenum was intended for neuronal histochemistry (total and metabolically active populations) and histological routine (morphometry and histopathology). The results showed more severe changes in neuronal density and intestinal morphometry in rats exposed to 20 ng/g, such as total neuronal density decrease and reduction of intestinal layers. In rats exposed to 600 ng/g of TBT, it was possible to observe only an increase in intraepithelial lymphocytes. We conclude that TBT can be more harmful to intestinal homeostasis when consumed in lower concentrations.
Effects of oral administration of ondansetron, a 5-HT receptor antagonist, on anxiety-related behaviors and colonic hypercontractility in repeated stress-induced mice.
Waemong A, Sattayachiti S, Cheaha D … +1 more , Konthapakdee N
Auton Neurosci · 2024 Jun · PMID 38642511 · Publisher ↗
PURPOSE: Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT receptors involves impairment of intestinal functions. This stud...
PURPOSE: Chronic psychological stress develops and exacerbates irritable bowel syndrome (IBS). 5-hydroxytryptamine (5-HT) via activation of intestinal 5-HT receptors involves impairment of intestinal functions. This study aimed to investigate the effects of ondansetron, a 5-HT receptor antagonist, on locomotor activity, anxiety-related behaviors, and colonic functions in repeated water avoidance stress. MATERIALS AND METHODS: Food intake and fecal pellet output (FPO) of sham stress (SS), water avoidance stress (WS), and water avoidance stress with oral administration of ondansetron (1 mg/kg BW) (WA) groups were monitored along the water avoidance stress protocol for 10 consecutive days. On day 11, locomotor activity and anxiety-related behaviors were determined using an open field test. Contractile properties of colonic tissues in response to KCl and a cumulative dose of carbachol (CCh) were determined using in vitro organ bath technique. RESULTS: FPO was significantly increased in the WS group after 7 days of water avoidance stress, which was reversed in WA group. WS group decreased unsupported rearing behavior compared to WS group, which was not altered in the WA group. The colon of the WS group had a higher tonic contraction in response to CCh than the SS and WA groups, which was reversed with ondansetron pre-incubation. CONCLUSIONS: Oral administration of ondansetron prevented increased FPO but did not affect anxiety-related behavior in repeated stress model. Colonic hypercontractility in the stressed mice was related to increased responses to cholinergic-induced contractions, which involved 5-HT receptors. Our findings suggest the modulatory roles of 5-HT receptors to mediate stress-induced colonic dysfunction.
Localization of sensory nerve terminals containing calcitonin gene-related peptide (CGRP) on striated muscle fibers in the rat esophagus: Evidence for triple innervation via motor endplates.
Kuramoto H, Yabe M, Morishita R … +2 more , Yoshimura R, Sakamoto H
Auton Neurosci · 2024 Jun · PMID 38636284 · Publisher ↗
BACKGROUND: Many esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on...
BACKGROUND: Many esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on a few striated muscle fibers in the rat esophagus, implying that these muscle fibers are triply innervated. In this study, we examined the localization and origin of CGRP-nerve endings in striated muscles to consider their possible roles in the esophagus regarding triple innervation. METHODS: Wholemounts of the rat esophagus were immunolabeled to detect CGRP-nerve endings in striated muscles. Also, retrograde tracing was performed by injecting Fast Blue (FB) into the esophagus, and cryostat sections of the medulla oblongata, nodose ganglion (NG), and the tenth thoracic (T10) dorsal root ganglion (DRG) were immunostained to identify the origin of the CGRP-nerve endings. RESULTS: CGRP-fine, varicose nerve endings were localized in motor endplates on a few esophageal striated muscle fibers (4 %), most of which received nitric oxide (NO) synthase nerve terminals, and most of the CGRP nerve endings were SP- and transient receptor potential vanilloid member 1 (TRPV1)-positive. Retrograde tracing showed many FB-labeled CGRP-neurons positive for SP and TRPV1 in the NG and T10 DGR. CONCLUSIONS: This study suggests that the CGRP-varicose nerve endings containing SP and TRPV1 in motor endplates are sensory, and a few esophageal striated muscle fibers are triply innervated. The nerve endings may detect acetylcholine-derived acetic acid from the vagal motor nerve endings and NO from esophageal intrinsic nerve terminals in the motor endplates to regulate esophageal motility.
Hepatic interoception in health and disease.
Berthoud HR, Münzberg H, Morrison CD … +1 more , Neuhuber WL
Auton Neurosci · 2024 Jun · PMID 38579493 · Full text
The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body vi...
The liver is a large organ with crucial functions in metabolism and immune defense, as well as blood homeostasis and detoxification, and it is clearly in bidirectional communication with the brain and rest of the body via both neural and humoral pathways. A host of neural sensory mechanisms have been proposed, but in contrast to the gut-brain axis, details for both the exact site and molecular signaling steps of their peripheral transduction mechanisms are generally lacking. Similarly, knowledge about function-specific sensory and motor components of both vagal and spinal access pathways to the hepatic parenchyma is missing. Lack of progress largely owes to controversies regarding selectivity of vagal access pathways and extent of hepatocyte innervation. In contrast, there is considerable evidence for glucose sensors in the wall of the hepatic portal vein and their importance for glucose handling by the liver and the brain and the systemic response to hypoglycemia. As liver diseases are on the rise globally, and there are intriguing associations between liver diseases and mental illnesses, it will be important to further dissect and identify both neural and humoral pathways that mediate hepatocyte-specific signals to relevant brain areas. The question of whether and how sensations from the liver contribute to interoceptive self-awareness has not yet been explored.
Small fiber neuropathy in children, adolescents, and young adults with chronic orthostatic intolerance and postural orthostatic tachycardia syndrome: A retrospective study.
Moak JP, Ramwell CB, Gordish-Dressman H … +2 more , Sule SD, Bettini E
Auton Neurosci · 2024 Jun · PMID 38537312 · Publisher ↗
PURPOSE: To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of ne...
PURPOSE: To determine in children, adolescent and young adult (CAYA) patients presenting with Orthostatic Intolerance (OI) or Postural Orthostatic Tachycardia Syndrome (POTS) associated with the additional symptoms of neuropathic discomfort (pain, paresthesia and/or allodynia): 1) the incidence of small fiber neuropathy, and 2) assess if there was serologic evidence for an underlying inflammatory or autoimmune state. METHODS: A cohort of 109 CAYA patients with the above symptoms underwent epidermal skin biopsy for nerve fiber density. Blood biomarkers for inflammation were tested (CRP, ESR, ANA, complement (C3), thyroid function testing with antibodies (thyroid peroxidase antibody and thyroglobulin antibody), and cytokine panel 13). Patients completed a Quality of Health questionnaire. Statistical analysis was performed using Wilcoxon rank sum tests. RESULTS: In CAYA patients with OI or POTS and neuropathic symptoms, skin biopsy for small fiber neuropathy was abnormal in 53 %. The sample population was predominantly female and Caucasian with moderately decreased perceived quality of health. OI /POTS patients with small fiber neuropathy had a 3-fold probability of having a positive ANA or anti-thyroid antibody, suggesting an underlying autoimmune or inflammatory process. CONCLUSION: Our data suggest a link between OI and POTS and small fiber neuropathy. Small fiber neuropathy was found by skin biopsy in over half of the patients tested. OI and Postural orthostatic tachycardia patients with small fiber neuropathy expressed multiple markers suggesting an underlying autoimmune or inflammatory process. Future research will be done to evaluate the symptomatic implication of SFN and whether immune or pharmacologic manipulation can alter patient symptoms.
Vagus nerve stimulation alleviates cardiac dysfunction and inflammatory markers during heart failure in rats.
Owens MM, Dalal S, Radovic A … +6 more , Fernandes L, Syed H, Herndon MK, Cooper C, Singh K, Beaumont E
Auton Neurosci · 2024 Jun · PMID 38513382 · Full text
Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of hea...
Vagus nerve stimulation (VNS) is under clinical investigation as a therapy for heart failure with reduced ejection fraction (HFrEF). This study aimed to investigate its therapeutic effects on three main components of heart failure: cardiac function, cardiac remodeling and central neuroinflammation using a pressure overload (PO) rat model. Male Sprague-Dawley rats were divided into four groups: PO, PO + VNS, PO + VNS sham, and controls. All rats, except controls, underwent a PO surgery to constrict the thoracic aorta (~50 %) to induce HFrEF. Open loop VNS therapy was continuously administered to PO + VNS rats at 20 Hz, 1.0 mA for 60 days. Evaluation of cardiac function and structure via echocardiograms showed decreases in stroke volume and relative ejection fraction and increases in the internal diameter of the left ventricle during systole and diastole in PO rats (p < 0.05). However, these PO-induced adverse changes were alleviated with VNS therapy. Additionally, PO rats exhibited significant increases in myocyte cross sectional areas indicating hypertrophy, along with significant increases in myocardial fibrosis and apoptosis, all of which were reversed by VNS therapy (p < 0.05). Furthermore, VNS mitigated microglial activation in two central autonomic nuclei: the paraventricular nucleus of the hypothalamus and locus coeruleus. These findings demonstrate that when VNS therapy is initiated at an early stage of HFrEF progression (<10 % reduction in relative ejection fraction), the supplementation of vagal activity is effective in restoring multi organ homeostasis in a PO model.
Gastrointestinal dysfunction in the valproic acid induced model of social deficit in rats.
Varley AN, Browning KN
Auton Neurosci · 2024 Jun · PMID 38461695 · Full text
Autism spectrum disorder (ASD) has increased in incidence over the past several decades, and is associated with a range of co-morbidities including gastrointestinal (GI) dysfunctions including gastroesophageal reflux, ab...
Autism spectrum disorder (ASD) has increased in incidence over the past several decades, and is associated with a range of co-morbidities including gastrointestinal (GI) dysfunctions including gastroesophageal reflux, abdominal pain, bloating, constipation and/or diarrhea. Several animal models have been used that replicate several aspects of ASD but no single model has been able to replicate the entire disease pathophysiology. In humans, prenatal exposure to valproic acid (VPA) has been identified as a significant risk factor and rodent models have shown that in utero VPA exposure leads to behavioral deficits in offspring. The present study aimed to investigate whether in utero exposure to VPA induces GI dysfunction in rats. Timed pregnant Sprague-Dawley rats were injected with a single dose of VPA at embryonic day 12.5. Both male and female offspring subsequently underwent behavioral studies and assessment of GI function in adulthood. In utero VPA treatment induced social deficits in both male and female offspring, decreasing sociability and social novelty. Histological examination showed that VPA treated offspring had decreased thickness of GI muscle and mucosa, while immunohistochemical studies showed a decrease in myenteric neuron number in the fundus. Functional studies showed that both male and female VPA offspring had a delay in gastric emptying compared to vehicle treated offspring. Results of the current study suggest that the rat VPA model of behavioral deficits may be a convenient model by which both mechanistic and functional insights into GI dysfunction may be studied.
Innate and adaptive immune system consequences of post-traumatic stress disorder.
Lauten TH, Natour T, Case AJ
Auton Neurosci · 2024 Apr · PMID 38428324 · Full text
In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopath...
In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked (though not fully proven) to the apparent dysregulation of the immune system after psychological trauma. To date, there is little to no evidence that demonstrates current PTSD therapies are able to reverse the increased risk for psychological trauma-induced inflammatory diseases, which suggests the behavioral and somatic consequences of PTSD may not be tightly coupled. This observation provides an opportunity to explore unique mechanisms outside of the brain that contribute to the long-term pathology of PTSD. Herein, we provide an overview of neuroimmune mechanisms, describe what is known regarding innate and adaptive immunity in PTSD, and suggest new directions that are needed to advance the understanding, diagnosis, and treatment of PTSD moving forward.
Assessment of cardiovascular functioning following sport-related concussion: A physiological perspective.
Ellingson CJ, Shafiq MA, Ellingson CA … +3 more , Neary JP, Dehghani P, Singh J
Auton Neurosci · 2024 Apr · PMID 38428323 · Publisher ↗
There is still much uncertainty surrounding the approach to diagnosing and managing a sport-related concussion (SRC). Neurobiological recovery may extend beyond clinical recovery following SRC, highlighting the need for...
There is still much uncertainty surrounding the approach to diagnosing and managing a sport-related concussion (SRC). Neurobiological recovery may extend beyond clinical recovery following SRC, highlighting the need for objective physiological parameters to guide diagnosis and management. With an increased understanding of the connection between the heart and the brain, the utility of assessing cardiovascular functioning following SRC has gained attention. As such, this review focuses on the assessment of cardiovascular parameters in the context of SRC. Although conflicting results have been reported, decreased heart rate variability, blood pressure variability, and systolic (ejection) time, in addition to increased spontaneous baroreflex sensitivity and magnitude of atrial contraction have been shown in acute SRC. We propose that these findings result from the neurometabolic cascade triggered by a concussion and represent alterations in myocardial calcium handling, autonomic dysfunction, and an exaggerated compensatory response that attempts to maintain homeostasis following a SRC. Assessment of the cardiovascular system has the potential to assist in diagnosing and managing SRC, contributing to a more comprehensive and multimodal assessment strategy.
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