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Annual Review of Immunology Jun 2024Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut... (Review)
Review
Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut homeostasis and modulation of inflammatory and infectious intestinal diseases. In this review, we describe the innervation of the intestine by intrinsic and extrinsic neurons and then focus on the bidirectional communication between neurons and immune cells. First, we highlight the contribution of neuronal subtypes to the development of colitis and discuss the different immune and epithelial cell types that are regulated by neurons via the release of neuropeptides and neurotransmitters. Next, we review the role of intestinal inflammation in the development of visceral hypersensitivity and summarize how inflammatory mediators induce peripheral and central sensitization of gut-innervating sensory neurons. Finally, we outline the importance of immune cells and gut microbiota for the survival and function of different neuronal populations at homeostasis and during bacterial and helminth infection.
Topics: Humans; Animals; Neuroimmunomodulation; Intestines; Homeostasis; Gastrointestinal Microbiome; Intestinal Mucosa; Neurons; Neuropeptides; Enteric Nervous System
PubMed: 38941607
DOI: 10.1146/annurev-immunol-101921-042929 -
Acta Paediatrica (Oslo, Norway : 1992) Jun 2024To investigate the role of autonomic nervous system in subpopulations of children with enuresis.
AIM
To investigate the role of autonomic nervous system in subpopulations of children with enuresis.
METHODS
We included 35 children with enuresis, divided in children with (17) and without nocturnal polyuria (18) and 43 healthy controls. For all participants hormones and neurotransmitters were measured. Patients and controls wore a sleep tracker device and children with enuresis underwent a 24 h blood pressure monitoring, nocturnal urine output measurement and uroflowmetry.
RESULTS
Children with enuresis had lower than controls copeptin and aldosterone, with the latter being more prominent in patients without nocturnal polyuria. Dopamine was lower in patients without nocturnal polyuria compared with patients with nocturnal polyuria. Children without polyuria experienced episodes only during NREM sleep, whereas in children with polyuria episodes occurred in both REM and NREM sleep. Children with enuresis experienced a non-dipping phenomenon during sleep which was more prominent in the group without polyuria.
CONCLUSION
In patients with nocturnal polyuria, nocturnal enuresis is associated with sympathetic hyperactivity which results in pressure polyuria and significantly lower systolic dipping during sleep. On the contrary, in children without nocturnal polyuria, it is mostly associated with bladder overactivity due to parasympathetic overstimulation as demonstrated by the NREM-related enuretic episodes and the lower aldosterone and dopamine levels.
PubMed: 38940196
DOI: 10.1111/apa.17338 -
Neuroscience Jun 2024The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic...
The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone.
PubMed: 38936460
DOI: 10.1016/j.neuroscience.2024.06.025 -
Langenbeck's Archives of Surgery Jun 2024The anatomical variations of the recurrent laryngeal nerve (RLN) are common during thyroidectomy. We aimed to evaluate the risk of RLN paralysis in case of its...
PURPOSE
The anatomical variations of the recurrent laryngeal nerve (RLN) are common during thyroidectomy. We aimed to evaluate the risk of RLN paralysis in case of its anatomical variations, retrospectively.
METHODS
The patients with primary thyroidectomy between January 2016 and December 2019 were enrolled. The effect of age, gender, surgical intervention, neuromonitorisation type, central neck dissection, postoperative diagnosis, neck side, extralaryngeal branching, non-RLN, relation of RLN to inferior thyroid artery (ITA), grade of Zuckerkandl tubercle on vocal cord paralysis (VCP) were investigated.
RESULTS
This study enrolled 1070 neck sides. The extralaryngeal branching rate was 35.5%. 45.9% of RLNs were anterior and 44.5% were posterior to the ITA, and 9.6% were crossing between the branches of the ITA. The rate of total VCP was 4.8% (transient:4.5%, permanent: 0.3%). The rates of total and transient VCP were significantly higher in extralaryngeal branching nerves compared to nonbranching nerves (6.8% vs. 3.6%, p = 0.018; 6.8% vs. 3.2%, p = 0.006, respectively). Total VCP rates were 7.2%, 2.5%, and 2.9% in case of the RLN crossing anterior, posterior and between the branches of ITA, respectively (p = 0.003). The difference was also significant regarding the transient VCP rates (p = 0.004). Anterior crossing pattern increased the total and transient VCP rates 2.8 and 2.9 times, respectively.
CONCLUSION
RLN crossing ITA anteriorly and RLN branching are frequent anatomical variations increasing the risk of VCP in thyroidectomy that cannot be predicted preoperatively. This study is the first one reporting that the relationship between RLN and ITA increased the risk of VCP.
Topics: Humans; Thyroidectomy; Female; Male; Vocal Cord Paralysis; Middle Aged; Retrospective Studies; Adult; Recurrent Laryngeal Nerve; Thyroid Gland; Aged; Recurrent Laryngeal Nerve Injuries; Risk Factors; Young Adult; Postoperative Complications; Adolescent
PubMed: 38935142
DOI: 10.1007/s00423-024-03392-y -
JACC. Clinical Electrophysiology Jun 2024The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF...
BACKGROUND
The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood.
OBJECTIVES
The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI).
METHODS
This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline.
RESULTS
A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups.
CONCLUSIONS
In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.
PubMed: 38934973
DOI: 10.1016/j.jacep.2024.04.035 -
Journal of the American Heart... Jul 2024Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological...
BACKGROUND
Rostral ventrolateral medulla (RVLM) neuron hyperactivity raises sympathetic outflow, causing hypertension. MicroRNAs (miRNAs) contribute to diverse biological processes, but their influence on RVLM neuronal excitability and blood pressure (BP) remains widely unexplored.
METHODS AND RESULTS
The RVLM miRNA profiles in spontaneously hypertensive rats were unveiled using RNA sequencing. Potential effects of these miRNAs in reducing neuronal excitability and BP and underlying mechanisms were investigated through various experiments. Six hundred thirty-seven miRNAs were identified, and reduced levels of miR-193b-3p and miR-346 were observed in the RVLM of spontaneously hypertensive rats. Increased miR-193b-3p and miR-346 expression in RVLM lowered neuronal excitability, sympathetic outflow, and BP in spontaneously hypertensive rats. In contrast, suppressing miR-193b-3p and miR-346 expression in RVLM increased neuronal excitability, sympathetic outflow, and BP in Wistar Kyoto and Sprague-Dawley rats. Cdc42 guanine nucleotide exchange factor ( was recognized as a target of miR-193b-3p. Overexpressing miR-193b-3p caused an evident decrease in expression, resulting in the inhibition of neuronal apoptosis. By contrast, its downregulation produced the opposite effects. Importantly, the decrease in neuronal excitability, sympathetic outflow, and BP observed in spontaneously hypertensive rats due to miR-193b-3p overexpression was greatly counteracted by upregulation.
CONCLUSIONS
miR-193b-3p and miR-346 are newly identified factors in RVLM that hinder hypertension progression, and the miR-193b-3p//apoptosis pathway presents a potential mechanism, highlighting the potential of targeting miRNAs for hypertension prevention.
Topics: Animals; MicroRNAs; Rats, Inbred SHR; Medulla Oblongata; Rats, Inbred WKY; Hypertension; Blood Pressure; Rats, Sprague-Dawley; Male; Disease Models, Animal; Rats; Rho Guanine Nucleotide Exchange Factors; Neurons; Sympathetic Nervous System; Apoptosis
PubMed: 38934856
DOI: 10.1161/JAHA.124.034965 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024To compare the effect of stage 3 fragmentation and the paradoxical phase of night sleep on melatonin (MT) secretion, and to evaluate the effects of changes in autonomic...
OBJECTIVE
To compare the effect of stage 3 fragmentation and the paradoxical phase of night sleep on melatonin (MT) secretion, and to evaluate the effects of changes in autonomic balance and activation reactions that occur in the orthodox and paradoxical phases of sleep.
MATERIAL AND METHODS
Fifteen healthy men participated in three sessions: with stage 3 fragmentation, with fragmentation of paradoxical sleep, and in a control experiment in which sleep was not disturbed. In each experiment, 7 saliva samples were collected in the evening, at night and in the morning and the MT content was determined. Heart rate variability was analyzed using an electrocardiogram and autonomic balance was assessed.
RESULTS
Sleep fragmentation was accompanied by activation reactions and reduced the duration of stage 3 and paradoxical phase sleep by 50% and 51% in the corresponding sessions. Fragmentation of paradoxical sleep also led to an increase in the duration of night wakefulness. Sleep disturbances caused an increase in MT secretion in the second half of the night and in the morning, especially pronounced in sessions with fragmentation of paradoxical sleep, in which upon awakening MT was 1.8 times higher than in the control. Stage 3 fragmentation was accompanied by increased sympathetic activation, while fragmentation of paradoxical sleep did not cause autonomic shifts. The subjects were divided into 2 clusters: with high and low MT in night and morning saliva samples. In all sessions, subjects with high MT had 1.7-2 times longer duration of night wakefulness; in sessions with fragmentation, they had significantly more activations in the paradoxical phase of sleep.
CONCLUSION
Night sleep disturbances cause an increase in MT secretion, especially pronounced during the fragmentation of the paradoxical phase. An increase in MT levels does not depend on changes in autonomic balance and is apparently associated with activation of the serotonergic system, which accompanies disturbances in the depth and continuity of sleep.
Topics: Humans; Melatonin; Male; Sleep, REM; Adult; Saliva; Sleep Deprivation; Sleep, Slow-Wave; Young Adult; Heart Rate; Autonomic Nervous System; Wakefulness
PubMed: 38934663
DOI: 10.17116/jnevro202412405226 -
Cureus Jun 2024This study investigated the pathogenesis and pathophysiology of chronic epipharyngitis, which presents a variety of symptoms, with a focus on autonomic neuropathy... (Review)
Review
This study investigated the pathogenesis and pathophysiology of chronic epipharyngitis, which presents a variety of symptoms, with a focus on autonomic neuropathy symptoms, and also investigated the literature for information on EAT, which is useful as a treatment method. The mechanism of action of EAT has recently been clarified in terms of its immune system-stimulating and endocrine system-stimulating effects. However, the autonomic nerve-stimulating effects of EAT are still largely unexplained. This study was conducted to collect and integrate previous studies and papers focusing on the autonomic nerve-stimulating effects of EAT and to provide insight into the still not fully elucidated autonomic nerve-stimulating effects of EAT on chronic epipharyngitis. The local stimulating effects of zinc chloride and the bleeding and pain effects of EAT are also summarized, suggesting that EAT exerts its therapeutic effects through the interaction of the immune system, the endocrine system, and the autonomic nervous system. It is important to determine which mechanism is predominantly involved in each case of chronic epipharyngitis and to utilize it in treatment. Elucidating the effects of EAT on the autonomic nervous system will be an important guideline in determining the treatment strategy for chronic epipharyngitis.
PubMed: 38933344
DOI: 10.7759/cureus.63182 -
Neurobiology of Stress Jul 2024High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS)...
High stress is a key risk factor for alcohol use disorder (AUD) and often accompanied by physiological dysregulation including autonomic nervous system (ANS) disruptions. However, neural mechanisms underlying drinking behaviors associated with stress and ANS disruptions remain unclear. The current study aims to understand neural correlates of stress, ANS disruptions, and subsequent alcohol intake in social drinkers with risky drinking. Using functional magnetic resonance imaging (fMRI), we investigated brain and heart rate (HR) autonomic responses during brief exposure to stress, alcohol, and neutral cues utilizing a well-validated, individualized imagery paradigm in 48 social drinkers of which 26 reported high-risk drinking (HD) while 22 reported low-risk drinking (LD) patterns. Results indicated that HD individuals showed stress and ANS disruptions with increased basal HR, stress-induced craving, and decreased brain response to stress exposure in frontal-striatal regions including the ventromedial prefrontal cortex (VmPFC), anterior cingulate cortex, striatum, insula, and temporal gyrus. Furthermore, whole-brain correlation analysis indicated that greater basal HR was associated with hypoactive VmPFC, but hyperactive medulla oblongata (MOb) responses during stress, with an inverse association between activity in the VmPFC and Mob (whole-brain corrected (WBC), p < 0.05). Functional connectivity with the MOb as a seed to the whole brain indicated that HD versus LD had decreased functional connectivity between the VmPFC and MOb during stress (WBC, p < 0.05). In addition, those with more compromised functional connectivity between the VmPFC and MOb during stress consumed greater amount of alcohol beverage during an experimental alcohol taste test conducted on a separate day, as well as in their self-reported weekly alcohol intake. Together, these results indicate that stress-related, dysfunctional VmPFC control over brain regions of autonomic arousal contributes to greater alcohol motivation and may be a significant risk factor for hazardous alcohol use in non-dependent social drinkers. Findings also suggest that restoring VmPFC integrity in modulating autonomic arousal during stress may be critical for preventing the development of AUD.
PubMed: 38933283
DOI: 10.1016/j.ynstr.2024.100645 -
Frontiers in Cardiovascular Medicine 2024Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in age-related...
OBJECTIVE
Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in age-related diseases, but its role in AF development remains unclear. This study aimed to investigate the correlations between changes in the autonomic nervous system, short-chain fatty acids (SCFAs), and alterations in gut microbiota in aged rats with AF.
METHODS
Electrophysiological experiments were conducted to assess AF induction rates and heart rate variability in rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify SCFAs in fecal samples.
RESULTS
The study found that aged rats exhibited a higher incidence of AF and reduced heart rate variability compared to young rats. Omics research revealed disrupted gut microbiota in aged rats, specifically a decreased Firmicutes to Bacteroidetes ratio. Additionally, fecal SCFA levels were significantly lower in aged rats. Importantly, correlation analysis indicated a significant association between decreased SCFAs and declining heart rate variability in aged rats.
CONCLUSIONS
These findings suggest that SCFAs, as metabolites of gut microbiota, may play a regulatory role in autonomic nervous function and potentially influence the onset and progression of AF in aged rats. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF.
PubMed: 38932988
DOI: 10.3389/fcvm.2024.1394929