Parasympathetic nervous system activity can downregulate inflammation, but it remains unclear how parasympathetic nervous system activity relates to antiviral activity. The present study examined associations between parasympathetic nervous system activity and cellular antiviral gene regulation in 90 adolescents (Mage = 16.28, SD = 0.73; 51.1% female) who provided blood samples and measures of cardiac respiratory sinus arrhythmia (RSA), twice, five weeks apart. Using a multilevel analytic framework, we found that higher RSA (an indicator of higher parasympathetic nervous system activity)-both at rest and during paced breathing-was associated with higher expression of Type I interferon (IFN) response genes in circulating leukocytes, even after adjusting for demographic and biological covariates. RSA was not associated with a parallel measure of inflammatory gene expression. These results identify a previously unrecognized immunoregulatory aspect of autonomic nervous system function and highlight a potential biological pathway by which parasympathetic nervous system activity may relate to health.

It is well-established that baroreflex sensitivity is essential for blood pressure control, and also plays a key role in the modulation of disease-induced metabolic alterations. In order to investigate the role of the baroreflex in the cardiometabolic and inflammatory derangements promoted by fructose overload, Wistar rats underwent sinoaortic denervation (SAD) or sham surgery and were studied 90 days after receiving tap water (Den and Ctrl) or a 10% fructose solution (Fruc and Den-Fruc). All experimental groups showed marked and similar degree of baroreflex impairment compared to Ctrl. As expected, fructose overload effectively induced metabolic syndrome; however, when it was associated with SAD, several alterations were attenuated. While Fruc rats displayed increased sympathetic modulation and tone and reduced vagal modulation compared to Ctrl animals, Den-Fruc rats showed greater vagal tone and modulation when compared to the Fruc group. Moreover, the Den-Fruc group showed augmented expression of β1 adrenergic receptors and TNF/IL-10 ratio and reduction of β2 in the left ventricle. The increase in vagal function was correlated with improved insulin sensitivity (r2 = 0.76), and decreased abdominal fat (r2 = -0.78) and β2 receptors (r2 = -0.85). Our results showed that: (1) chronic fructose overload induced severe baroreflex impairment, i.e. in a similar magnitude to that observed in SAD rats, which is accompanied by cardiometabolic dysfunctions; (2) the compensatory enhancement in parasympathetic function in SAD rats submitted to fructose intake may point out the possibility of use of approaches that improve vagal function as therapeutic target to attenuate fructose-induced cardiometabolic dysfunctions.

Although the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown.

The aim of this study was to investigate the training-induced effect on cardiac parasympathetic nervous system (PNS) activity, assessed by resting heart rate variability (HRV) and post-exercise heart rate recovery (HRR), in sedentary healthy people. Electronic searches were carried out in PubMed, Embase, and Web of Science. Random-effects models of between-group standardised mean difference (SMD) were estimated. Heterogeneity analyses were performed by means of the chi-square test and I2 index. Subgroup analyses and meta-regressions were performed to investigate the influence of potential moderator variables on the training-induced effect. The results showed a small increase in RMSSD (SMD+ = 0.57 [95% confidence interval (CI) = 0.23, 0.91]) and high frequency (HF) (SMD+ = 0.21 [95% CI = 0.01, 0.42]) in favour of the intervention group. Heterogeneity tests reached statistical significance for RMSSD and HF (p ≤ 0.001), and the inconsistency was moderate (I2 = 68% and 60%, respectively). We found higher training-induced effects on HF in studies that performed a shorter intervention or lower number of exercise sessions (p ≤ 0.001). Data were insufficient to investigate the effect of exercise training on HRR. Exercise training increases cardiac PNS modulation in sedentary people, while its effect on PNS tone requires future study.

The gut microbiota has been demonstrated to play a critical role in maintaining cognitive function via the gut-brain axis, which may be related to the parasympathetic nervous system (PNS). However, the exact mechanism remains to be determined. We investigated that patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) could exhibit an altered gut microbiota through the suppression of the PNS, compared to the healthy individuals, using the combined gut microbiota data from previous human studies. The hypothesis was validated in rats to suppress the PNS by scopolamine injections. The human fecal bacterial FASTA/Q files were selected and combined from four different AD studies (n = 410). All rats had a high-fat diet and treatments for six weeks. The MD rats had memory impairment by scopolamine injection (2 mg/kg body weight; MD, Control) or no memory impairment by saline injection. The scopolamine-injected rats had a donepezil intake as the positive group. In the optimal model generated from the XGboost analysis, Blautia luti, Pseudomonas mucidoiens, Escherichia marmotae, and Gemmiger formicillis showed a positive correlation with MCI while Escherichia fergusonii, Mycobacterium neglectum, and Lawsonibacter asaccharolyticus were positively correlated with AD in the participants with enterotype Bacteroides (ET-B, n = 369). The predominant bacteria in the AD group were negatively associated in the networking analysis with the bacteria in the healthy group of ET-B participants. From the animal study, the relative abundance of Bacteroides and Bilophilia was lower, and that of Escherichia, Blautia, and Clostridium was higher in the scopolamine-induced memory deficit (MD) group than in the normal group. These results suggest that MCI was associated with the PNS suppression and could progress to AD by exacerbating the gut dysbiosis. MCI increased Clostridium and Blautia, and its progression to AD elevated Escherichia and Pseudomonas. Therefore, the modulation of the PNS might be linked to an altered gut microbiota and brain function, potentially through the gut-brain axis.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.

Although sympathetic hyperactivity with preserved parasympathetic activity has been extensively recognized in fatal familial insomnia (FFI), the symptoms of parasympathetic nervous system failure observed in some patients are difficult to explain. Using heart rate variability (HRV), this study aimed to discover evidence of parasympathetic dysfunction in patients with FFI and the difference of parasympathetic activity between patients with FFI and Creutzfeldt-Jakob disease (CJD).

Heart rate is controlled by the activity of the autonomic nervous system: the sympathetic and parasympathetic nervous systems increase and suppress heart rate, respectively. To evaluate the activity of the autonomic nervous system, it is possible to determine heart rate variability using electrocardiography (ECG). During the fetal period, the heart and autonomic nerves develop in coordination; however, physiological changes, including autonomic nervous activities that occur during the fetal stage, remain largely unknown. Therefore, in this study, we measured ECG signals of mouse fetuses using our established method to evaluate the development of heart rate and autonomic nervous activity at different fetal developmental stages. We found that heart rate was significantly increased in fetal mice at embryonic day (E) 18.5 compared with that at E13.5, E15.5, and E17.5, indicating that fetal heart rate increases only at the stage immediately prior to birth. Interestingly, fetal parasympathetic nervous activity was reduced at E17.5 and E18.5 compared with that at E13.5, whereas fetal sympathetic nervous activity remained unchanged, at least from E13.5 to E18.5. These results indicate that parasympathetic activity rather than sympathetic activity affects fetal heart rate and that the decrease in parasympathetic activity toward the end of pregnancy could result in the observed increase in fetal heart rate.

The vagus nerve mediates parasympathetic nervous system control of peripheral physiological processes including cardiovascular activity and immune response. In mice, tonic vagal activation down-regulates inflammation via nicotinic acetylcholine receptor-mediated inhibition of the pro-inflammatory transcription factor NF-κB in monocyte/macrophages. Because Type I interferon and pro-inflammatory genes are regulated reciprocally at the level of transcription factor activation and cell differentiation, we hypothesized that vagal activity would up-regulate Type I interferon response genes concurrently with inflammatory downregulation in human immune cells. We mapped empirical individual differences in the circulating leukocyte transcriptome and vagal activity indexed by high frequency (0.15-0.40 Hz) heart rate variability (HF-HRV) in 380 participants in the Midlife in the US study. Here we show that promoter-based bioinformatics analyses linked greater HF-HRV to reduced NF-κB activity and increased activity of IRF transcription factors involved in Type I interferon response (independent of β-antagonists, BMI, smoking, heavy alcohol consumption, and demographic factors). Transcript origin analyses implicated myeloid lineage immune cells as targets, representing per-cell alterations in gene transcription as HF-HRV was not associated with differential prevalence of leukocyte subsets. These findings support the concept of parasympathetic inhibition of pro-inflammatory gene expression in humans and up-regulation of Type I interferons that could augment host defense against viral infections.

Background: Autonomic nervous system (ANS) dysfunction has been suggested to contribute to the high prevalence of cardiovascular complications in individuals with anorexia nervosa (AN), yet has not been thoroughly investigated. The current review aimed to synthesize the evidence of basal ANS function in individuals with a current diagnosis of AN and those with a previous diagnosis who had achieved weight restoration, as compared to controls. Methods: A systematic review of nine databases was conducted and studies that were published in a peer-review journal, in English, that included at least one assessment of ANS function in individuals with a current or previous diagnosis of AN were selected. Forty-six studies were included with a total of 811 participants with a current diagnosis of AN and 123 participants with a previous diagnosis of AN. Results: ANS function was assessed through heart rate variability (n = 27), orthostatic challenge, blood pressure variability or baroreflex sensitivity (n = 11), adrenergic activity (n = 14), skin conductance level (n = 4), and pupillometry (n = 1). Individuals with AN demonstrated increased parasympathetic activity and decreased sympathetic activity, suggestive of autonomic dysregulation. Following weight restoration, autonomic function trended toward, or was equivalent to, control levels. Discussion: Autonomic dysregulation is indicated through a range of assessments in individuals with AN. Future investigations should utilize a variety of assessments together in order to conclusively establish the nature of autonomic dysfunction in AN, and following extended weight restoration. Moreover, investigation into the co-occurrence of ANS function and cardiovascular risk is required.

Delivery is not easily predictable in horses and the consequences of dystocia can be serious for both the mare and foal. An induction protocol with low doses of oxytocin has been reported as a safe procedure. This study investigates the effect of induced delivery on at-term mares' sympathetic-vagal balance. Fourteen mares were included and divided into two groups, one subjected to spontaneous delivery (SD), and one to induced delivery (ID). In both groups, an ECG was recorded using an elastic belt with integrated smart textile electrodes. The recording started before the delivery (Basal), continued close to delivery (Pre-delivery) and during delivery (Delivery), and ended after parturition (Placental expulsion). From the ECGs, Heart Rate Variability (HRV) parameters relating to time and frequency domains and non-linear analysis were extrapolated. The HRV analysis was performed both within the same group (IntraGA) and between the two groups (InterGA). In the present study, spontaneous and induced delivery did not appear to differ in autonomic nervous system functioning. In IntraGA analysis, both for SD and ID mares, delivery and placental expulsion periods were parasympathetic dominated since vagal-related HRV parameters increased. Moreover, no differences were found in InterGA comparison between SD and ID mares, except for the pre-delivery period of ID mares, during which both branches of the autonomic nervous system were activated. These results are in line with the literature on parasympathetic dominance during parturition and no change in Heart Rate Variability following exogenous oxytocin administration in parturient mares.

Research suggests that children's health and well-being are supported by core adaptive systems, including the autonomic nervous system (ANS). Despite evidence for the importance of adulthood ANS regulation in the development of disease, few studies have examined how early development may influence emerging ANS function. Therefore, we examined how infant adiposity gain during early infancy related to ANS regulation at 6 months.

In the intensive care and perioperative setting, circulation is often supported by intravenous fluid preceded by prediction of fluid responsiveness during a passive leg raising (PLR) maneuver. An increase in stroke volume (SV) or cardiac output (CO) of 10%-15% indicates that the subject may increase the flow upon volume expansion. However, the semi-recumbent position as an initial position in PLR likely reduces SV by gravitational displacement of central blood volume (CBV) to lower extremities, thereby accentuating volume responsiveness during leg raising in healthy people. Coincident with gravitational perturbations in hemodynamics, remedial changes occur in the autonomic nervous system (ANS), as expressed in spectral power in heart rate variability (HRV). This study aims to clarify these concomitant changes during PLR. A convenience number of healthy volunteers (N = 11) were recruited by advertisement in university departments. The subjects were exposed to the established PLR sequence and the heart rate (HR), mean arterial pressure (MAP), SV, and CO were sampled at 1 Hz, while electrocardiogram was recorded at 1000 Hz. Relative powers reflecting autonomic nervous system activity were assessed from spectral analysis of HRV. In response to PLR, SV increased (12.4% ± 8.7%, p < 0.0026), while HR (-7.6% ± 4.7%, p < 0.0009) and MAP (-7.6% ± 6.9%, p < 0.01) decreased, with no change in CO (4.1% ± 12.8%, ns). The HRV low-frequency component was reduced (-34%; p < 0.0095), while the high-frequency activity increased (78.5%; p < 0.0013), with a 63% decrease in the low/high frequency ratio (p < 0.0078). Thus, HRV indicated a reduced sympathetic index (semi-recumbent 0.808 vs. PLR -0.177 a.u., p < 0.001) and an increased parasympathetic index (-0.141 to 0.996 a.u., p < 0.0001). Gravitational depletion and expansion of CBV during PLR were associated with a counterregulatory autonomic response. Healthy volunteers appeared volume responsive in terms of SV, but not CO. Responses to PLR are influenced by the ANS, and HRV analysis should be included in the assessment of the PLR test.

The evolutionarily highly conserved neuropeptide oxytocin seems to be involved in the regulation of complex forms of social behavior. It enhances the processing of positive social stimuli, reduces behavioral and neuroendocrine stress responses and modulates amygdala activity in humans. Moreover, it has been proposed that oxytocin dampens sympathetic nervous system activity. This hypothesis was tested in a double-blind, placebo-controlled study with 38 men either receiving 24 IU oxytocin intranasally or a placebo spray. While accomplishing an emotion classification task, electrodermal responses were measured as an index of sympathetic activity. Moreover, heart rate changes were recorded that are additionally mediated by the parasympathetic nervous system. Oxytocin enhanced differential heart rate responses to facial expressions as a function of the emotional valence, but had no effect on electrodermal activity or tonic measures of physiological arousal. These results indicate that oxytocin specifically modulates phasic activity of the parasympathetic nervous system which potentially reflects an increased motivational value of facial expressions following oxytocin treatment. Findings suggest that anxiolytic effects of oxytocin are not reflected in short-term sympathetic responses and may even be a consequence of rather than a prerequisite for improved social information processing.

In the present immunohistochemical study the distribution of nitric oxide synthase (NOS) was studied in various autonomic ganglia and in related peripheral tissues of the rat. For comparison some other neuronal markers including acetylcholinesterase and tyrosine hydroxylase as well as several neuropeptides were analysed on adjacent or the same sections. The distribution of NOS-like immunoreactivity (LI) and of these other markers has been semiquantitatively summarized. In some parasympathetic ganglia such as the sphenopalatine and submandibular ganglia NOS-LI was present in most ganglion cells, at least partly coexisting with peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP) and neuropeptide tyrosine (NPY). In the pelvic ganglia a comparatively smaller proportion of neurons was NOS-positive and they often contained VIP-LI and less frequently NPY-LI. In the tissues innervated by these ganglia, such as nasal mucosa and salivary glands, NOS-positive fibers were observed around blood vessels and within the glandular parenchyma, although generally less abundant than VIP/PHI nerves, while in the uterus, vas deferens and penis a more close correlation was seen. NOS-positive fibers were also widely distributed in other tissues. In the sympathetic ganglia NOS-LI was mainly present in dense fiber networks, which disappeared after transection of the sympathetic trunc central to the ganglion. Since many cell bodies in the sympathetic lateral column of the spinal cord also were NOS-positive, it is likely that the majority of preganglionic fibers innervating sympathetic ganglia are NOS-positive. VIP-positive cells in stellate ganglia did not contain NOS-LI. The present results suggest that NO may be a messenger molecule both in parasympathetic postganglionic neurons and in preganglionic sympathetic neurons.

During entrance into torpor heart and respiration rates are greatly reduced in parallel with the reduction of metabolic rate, suggesting an involvement of parasympathetic control. We compared the effect of parasympathetic inhibition with the effect of sympathetic inhibition on spontaneous torpor behaviour in the Djungarian hamster. Hamsters were acclimated to short photoperiod and displayed their standard torpor pattern as observed from T(b) records. Parasympathetic inhibition was achieved by a subcutaneous implant of 21-day release pellets with Atropine and the sympathetic noradrenergic pathway was inhibited with a single injection of 6-Hydroxydopamine. Atropine treatment did not affect the occurrence and quality of spontaneous daily torpor at all. However, the reversible sympathetic inhibition by 6-Hydroxydopamine injection resulted in a complete disappearance of torpor for about 6 days. These results conclude that the onset of daily torpor requires an intact noradrenergic signalling of the sympathetic nervous system. We further observed that parasympathetic as well as sympathetic blockade resulted in an immediate abolishment of ultradian rhythms of body temperature. This suggests that the expression of ultradian oscillations in body temperature require a continued interaction of sympathetic and parasympathetic activity.

Self-induced cognitive trance (SICT) is a voluntary non-ordinary state of consciousness characterized by a lucid yet narrowed awareness of the external surroundings. It involves a hyper-focused immersive experience of flow, expanded inner imagery, modified somatosensory processing, and an altered perception of self and time. SICT is gaining attention due to its potential clinical applications. Similar states of non-ordinary state of consciousness, such as meditation, hypnosis, and psychedelic experiences, have been reported to induce changes in the autonomic nervous system. However, the functioning of the autonomic nervous system during SICT remains poorly understood. In this study, we aimed to investigate the impact of SICT on the cardiac and respiratory signals of 25 participants proficient in SICT. To accomplish this, we measured various metrics of heart rate variability (HRV) and respiration rate variability (RRV) in three conditions: resting state, SICT, and a mental imagery task. Subsequently, we employed a machine learning framework utilizing a linear discriminant analysis classifier and a cross-validation scheme to identify the features that exhibited the best discrimination between these three conditions. The results revealed that during SICT, participants experienced an increased heart rate and a decreased level of high-frequency (HF) HRV compared to the control conditions. Additionally, specific increases in respiratory amplitude, phase ratio, and RRV were observed during SICT in comparison to the other conditions. These findings suggest that SICT is associated with a reduction in parasympathetic activity, indicative of a hyperarousal state of the autonomic nervous system during SICT.

The proventriculus constitutes the glandular region of the chicken stomach. This organ is innervated by two parasympathetic networks, the myenteric and submucous plexus, and here we present a systematic study of this system by immunohistochemistry and electron microscopy. All the neurons and fibres were positive for the neural markers, protein gene product 9.5 and the amidating enzymes. Immunoreactivities for the constitutive neuronal isoform of the enzyme nitric oxide synthase and the vasoactive intestinal peptide were present in neuronal bodies suggesting an intrinsic origin for the similarly immunoreactive fibres found in the proventriculus. On the other hand, immunoreactivity to gastric inhibitory peptide was only found in varicose fibres making contact with the blood vessels and the glandular epithelium, but never in the neuronal somas, suggesting that this substance may be provided by an extrinsic nervous system whose neuronal bodies are located elsewhere. Electron microscopy revealed frequent neuromuscular and neuroepithelial connections in the muscle layers, the wall of the blood vessels and the epithelium. In addition, synapsis-like structures were identified in the proximity of cells belonging to the diffuse endocrine system, providing a new example of neuroendocrine contacts. No positivity was found for antibodies against other neural substances including somatostatin, peptide histidine-isoleucine, peptide tyrosine-tyrosine, neuropeptide tyrosine, bombesin, met-enkephalin, serotonin, substance P, galanin, calcitonin gene-related peptide and S-100 protein.

The autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS's pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS. Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.