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PloS One 2023Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their...
Dysfunction of peripheral somatic and autonomic nervous system in patients with severe forms of Crohn's disease on biological therapy with TNFα inhibitors-A single center study.
OBJECTIVE
Crohn's disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy.
MATERIAL AND METHODS
A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy.
RESULTS
Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn's Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test).
CONCLUSIONS
This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.
Topics: Humans; Crohn Disease; Autonomic Nervous System Diseases; Tumor Necrosis Factor-alpha; Autonomic Nervous System; Peripheral Nervous System Diseases; Biological Therapy
PubMed: 37967139
DOI: 10.1371/journal.pone.0294441 -
Developmental Dynamics : An Official... Aug 2023The molecular identification of neural progenitor cell populations that connect to establish the sympathetic nervous system (SNS) remains unclear. This is due to...
BACKGROUND
The molecular identification of neural progenitor cell populations that connect to establish the sympathetic nervous system (SNS) remains unclear. This is due to technical limitations in the acquisition and spatial mapping of molecular information to tissue architecture.
RESULTS
To address this, we applied Slide-seq spatial transcriptomics to intact fresh frozen chick trunk tissue transversely cryo-sectioned at the developmental stage prior to SNS formation. In parallel, we performed age- and location-matched single cell (sc) RNA-seq and 10× Genomics Visium to inform our analysis. Downstream bioinformatic analyses led to the unique molecular identification of neural progenitor cells within the peripheral sympathetic ganglia (SG) and spinal cord preganglionic neurons (PGNs). We then successfully applied the HiPlex RNAscope fluorescence in situ hybridization and multispectral confocal microscopy to visualize 12 gene targets in stage-, age- and location-matched chick trunk tissue sections.
CONCLUSIONS
Together, these data demonstrate a robust strategy to acquire and integrate single cell and spatial transcriptomic information, resulting in improved resolution of molecular heterogeneities in complex neural tissue architectures. Successful application of this strategy to the developing SNS provides a roadmap for functional studies of neural connectivity and platform to address complex questions in neural development and regeneration.
Topics: Animals; Transcriptome; RNA, Messenger; In Situ Hybridization, Fluorescence; Sympathetic Nervous System; Ganglia, Sympathetic; Chickens
PubMed: 36840366
DOI: 10.1002/dvdy.577 -
Current Cardiology Reports Jun 2024More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic... (Review)
Review
PURPOSE OF REVIEW
More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed.
RECENT FINDINGS
Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.
Topics: Humans; Sympathectomy; Chagas Cardiomyopathy; Arrhythmias, Cardiac; Heart; 3-Iodobenzylguanidine; Sympathetic Nervous System
PubMed: 38656586
DOI: 10.1007/s11886-024-02057-y -
Autoimmunity Reviews Nov 2023The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is... (Review)
Review
BACKGROUND
The Long-COVID syndrome constitutes a plethora of persisting symptoms with neurological disorders being the most disabling ones. The pathogenesis of Long-COVID is currently under heavy scrutiny and existing data on the role of auto-immune reaction to G-protein coupled receptors (GPCR) are conflicting.
METHODS
This monocentric, cross-sectional study included patients who suffered a mild to moderate SARS-CoV-2 infection up to 12 months prior to enrollment with (n = 72) or without (n = 58) Long-COVID diagnosis according to the German S1 guideline or with no known history of SARS-CoV-2 infection (n = 70). While autoantibodies specific for the vasoregulation associated Adrenergic Receptor (ADR) B1 and B2 and the CNS and vasoregulation associated muscarinic acetylcholine receptor (CHR) M3 and M4 were measured by ELISA, neurological disorders were quantified by internationally standardized questionnaires.
RESULTS
The prevalence and concentrations of evaluated autoantibodes were significantly higher in Long-COVID compared to the 2 other groups (p = 2.1*10) with a significantly higher number of patients with simultaneous detection of more than one autoantibody in the Long-COVID group (p = 0.0419). Importantly, the overall inflammatory state was low in all 3 groups. ARB1 and ARB2 correlated negatively CERAD Trail Marking A and B (R ≤ -0.26, p ≤ 0.043), while CHRM3 correlated positively with Chadler Fatigue Scale (R = 0.37, p = 0.0087).
CONCLUSIONS
Concentrations of autoantibodies correlates to the intensity of neurological disorders including psychomotor speed, visual search, attention, and fatigue.
Topics: Humans; Post-Acute COVID-19 Syndrome; COVID-19; Cross-Sectional Studies; SARS-CoV-2; Autoantibodies; Autonomic Nervous System; Fatigue; Nervous System Diseases; Receptor, Muscarinic M3
PubMed: 37689093
DOI: 10.1016/j.autrev.2023.103445 -
Psychophysiology Dec 2023Positive associations have been found between cortical thickness and measures of parasympathetic cardiac control (e.g., respiratory sinus arrhythmia, RSA) in adults,...
Positive associations have been found between cortical thickness and measures of parasympathetic cardiac control (e.g., respiratory sinus arrhythmia, RSA) in adults, which may indicate mechanistic integration between neural and physiological indicators of stress regulation. However, it is unknown when in development this brain-body association arises and whether the direction of association and neuroanatomical localization vary across development. To investigate this, we collected structural magnetic resonance imaging and resting-state respiratory sinus arrhythmia data from children in middle childhood (N = 62, M = 10.09, range: 8.28-12.14 years). Whole-brain and exploratory ROI analyses revealed positive associations between RSA and cortical thickness in four frontal and parietal clusters in the left hemisphere and one cluster in the right. Exploratory ROI analyses revealed a similar positive association between cortical thickness and RSA, with two regions surviving multiple comparison correction, including the inferior frontal orbital gyrus and the Sylvian fissure. Prior work has identified these cortical areas as part of the central autonomic network that supports integrative regulation of stress response (e.g., autonomic, endocrine, and behavioral) and emotional expression. Our results suggest that the association between cortical thickness and resting RSA is present in middle childhood and is similar to the associations seen during adulthood. Future studies should investigate associations between RSA and cortical thickness among young children and adolescents.
Topics: Adult; Adolescent; Humans; Child; Child, Preschool; Parasympathetic Nervous System; Heart; Respiratory Sinus Arrhythmia; Autonomic Nervous System; Brain
PubMed: 37455342
DOI: 10.1111/psyp.14391 -
Development and Psychopathology May 2024This study investigated the role of autonomic nervous system (ANS) coordination in response to emotion in girls' and boys' development of relational (e.g., ignoring,...
This study investigated the role of autonomic nervous system (ANS) coordination in response to emotion in girls' and boys' development of relational (e.g., ignoring, excluding) and physical (e.g., hitting, kicking) aggression. Caregivers reported on children's relational and physical aggression at ages 6, 7, 8, and 10 years ( = 232, 50.4% girls, 46.6% Latinx). Sympathetic nervous system (assessed via pre-ejection period) and parasympathetic nervous system (assessed via respiratory sinus arrhythmia) reactivity were measured in response to video clips depicting fear, happiness, and sadness at age 7. Growth curve models indicated that ANS reactivity to sadness, but not to fear or happiness, was related to trajectories of relational aggression. In contrast, ANS reactivity to all three emotions was associated with trajectories of physical aggression. Effects differed across genders, indicating that distinct patterns of ANS reactivity to emotion may be involved in girls' and boys' development of aggression. Overall, these findings contribute to a growing literature documenting the role of ANS reactivity to emotion in aggressive behavior. Moreover, this study considers ANS reactivity to specific emotions, as related to both relational and physical aggression, and as differentially expressed among girls versus boys.
Topics: Humans; Male; Female; Aggression; Child; Autonomic Nervous System; Emotions; Respiratory Sinus Arrhythmia; Fear; Sadness; Happiness; Parasympathetic Nervous System
PubMed: 36734227
DOI: 10.1017/S095457942200150X -
Clinical Autonomic Research : Official... Aug 2023Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of... (Review)
Review
PURPOSE
Cardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.
METHODS
Data from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clinical practice are summarized.
RESULTS
A harmonic interplay between the heart and the autonomic nervous system exists at multiple levels of the neuraxis. This interplay becomes disrupted in the setting of cardiovascular disease, resulting in pathological changes at multiple levels, from subcellular cardiac signaling of neurotransmitters to extra-cardiac, extra-thoracic remodeling. The subsequent detrimental cycle of sympathovagal imbalance, characterized by sympathoexcitation and parasympathetic withdrawal, predisposes to ventricular arrhythmias, progression of heart failure, and cardiac mortality. Knowledge on the etiology and pathophysiology of this condition has increased exponentially over the past few decades, resulting in a number of different neuromodulatory approaches. However, significant knowledge gaps in both sympathetic and parasympathetic interactions and causal factors that mediate progressive sympathoexcitation and parasympathetic dysfunction remain.
CONCLUSIONS
Although our understanding of autonomic imbalance in cardiovascular diseases has significantly increased, specific, pivotal mediators of this imbalance and the recognition and implementation of available autonomic parameters and neuromodulatory therapies are still lagging.
Topics: Humans; Autonomic Nervous System; Heart; Arrhythmias, Cardiac; Heart Failure; Cardiovascular Diseases; Primary Dysautonomias; Ventricular Function
PubMed: 37166736
DOI: 10.1007/s10286-023-00948-8 -
Journal of Neuroinflammation Nov 2023Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common...
BACKGROUND
Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma.
METHODS
Sox10/Rpl22 mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH sympathetic neurons and glial-restricted Sox10/JellyOP/Rpl22 mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI.
RESULTS
With ~ 4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glial reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic-driven enteric glial reactivity.
CONCLUSIONS
Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.
Topics: Animals; Mice; Gliosis; Adrenergic Agents; Neuroglia; Signal Transduction; Sympathetic Nervous System; Enteric Nervous System
PubMed: 37941007
DOI: 10.1186/s12974-023-02937-0 -
Psychoneuroendocrinology Apr 2024While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous...
While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous system (ANS) associated with PTSD, remains incompletely understood. During neutral and personalized trauma script imagery heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) were recorded in youth aged 8-18 with PTSD or partial PTSD (n = 76) and trauma-exposed controls (TEC) (n = 27) to determine ANS activity and stress reactivity. Within the patient group, 77.6% met the full DSM-IV diagnostic criteria for PTSD, the remaining 22.4% met the criteria for partial PTSD. Youth with (partial) PTSD were subsequently treated with eight sessions of either trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing. PTSD severity was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide patients into responders and non-responders. Youth with (partial) PTSD relative to TEC had higher overall HR during both neutral and trauma imagery (p = .05). Youth with (partial) PTSD showed RSA decrease during trauma imagery relative to neutral imagery, the reverse of TEC (p = .01). Relative to non-responders, responders demonstrated a significant baseline to posttreatment increase of RSA response to stress only when employing a ≥ 50% response criterion (p = .05) and not with the primary ≥ 30% criterion (p = .12). Our results suggest overall higher HR and sympathetic nervous system activity as well as vagal withdrawal in response to stress in youth with (partial) PTSD and only provide partial support for normalization of the latter with successful trauma-focused psychotherapy.
Topics: Child; Humans; Adolescent; Stress Disorders, Post-Traumatic; Psychotherapy; Cognitive Behavioral Therapy; Nervous System Physiological Phenomena; Autonomic Nervous System
PubMed: 38244488
DOI: 10.1016/j.psyneuen.2023.106945 -
Biological Psychology Feb 2024Intermittent fasting has been associated with diverse physical and psychological health benefits. According to previous research, fasting-induced alterations in...
Intermittent fasting has been associated with diverse physical and psychological health benefits. According to previous research, fasting-induced alterations in psychophysiological functioning should facilitate the accurate detection of an internal bodily signal (like the heart), which is referred to as interoceptive accuracy. In two within-subjects studies we aimed to examine whether an intermittent fasting protocol (i) evokes distinct autonomic nervous system changes in the laboratory and (ii) improves (objectifiable) interoceptive accuracy and sensibility (i.e., the subjective belief in perceiving bodily signals) in everyday life. Study 1 (N = 36) found increasing heart rate variability (precisely, the root mean square of successive differences; RMSSD) accompanied by a more vascular than myocardial response following a 16 h fast. Study 2 (N = 40) applied an ecological momentary assessment design including intermittent fasting (8 h normal eating followed by 16 h fasting) and normal eating (24 h normal eating) for three consecutive days each. Findings suggested a tendency toward higher interoceptive accuracy and sensibility during the fasting regimen, which was particularly pronounced in individuals exhibiting lower RMSSD. Together, findings suggest that (short-term) fasting seems to facilitate momentary attention to organismic cues due to alterations in autonomic nervous system function.
Topics: Humans; Interoception; Heart; Autonomic Nervous System; Fasting; Heart Rate; Awareness
PubMed: 38331345
DOI: 10.1016/j.biopsycho.2024.108760