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Biomedicines
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Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets
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Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 8859

Special Issue Editors

Dr. De-Pei Li

E-Mail Website
Guest Editor
Department of Medicine, Center for Precision Medicine, University of Missouri, Columbia, MO 65203, USA
Interests: autonomic nervous system; synaptic plasticity in neurological disorders; Ion channel
Prof. Dr. Zixi Cheng

E-Mail Website
Guest Editor
UCF College of Medicine, Orlando, FL, USA
Interests: cardiovascular autonomic nerve innervation; digestive system autonomic innervation; gut-brain interaction

Special Issue Information

Dear Colleagues,

The dysfunction of the autonomic nervous system is associated with many neurological diseases as a consequence or causality of primary diseases. Studies have been carried out to determine the mechanisms of dysautonomia in neurological disorders such as Alzheimer’s disease, Parkinson’s disease, depression, and neurogenic hypertension. In addition, dysautonomia also importantly contributes to metabolic diseases, such as diabetes, obesity, and metabolic syndrome, because it may lead to insulin resistance, altered lipid metabolism, and hypertension in metabolic syndrome. In a certain sensorium, autonomic dysfunction is associated with multiple diseases (e.g., diabetes mellitus and depression), suggesting that autonomic dysfunction is possibly a common mechanism that governs their pathological process. However, the role of autonomic dysfunction in creating or maintaining the pathology of neurological diseases is not still completely understood. Recovering altered autonomic function provides a potential therapy that can be used to treat certain neurological diseases. This Special Issue invites investigators to contribute original research articles and review articles that will help us understand the novel mechanisms of autonomic dysfunction in neurological diseases. Potential topics include, but are not limited to, the following: autonomic dysfunction in neurological disorders (such as Alzheimer's disease, Parkinson's disease, and depression); dysautonomia in insulin resistance in metabolic diseases; and dysautonomia in response to external environmental changes (such as stress, traumatic brain injury, or hormonal imbalances).

Dr. De-Pei Li
Prof. Dr. Zixi Cheng
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sympathetic nervous system
  • parasympathetic nervous system
  • novel mechanisms
  • novel molecular
  • genetic predisposition

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Published Papers (4 papers)

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Research

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20 pages, 2507 KiB  
Article
Cellular and Molecular Mechanisms Underlying Altered Excitability of Cardiac Efferent Neurons in Cirrhotic Rats
by Choong-Ku Lee, Huu Son Nguyen, Seong Jun Kang and Seong-Woo Jeong
Biomedicines 2024, 12(8), 1722; https://doi.org/10.3390/biomedicines12081722 - 1 Aug 2024
Viewed by 1118
Abstract
Patients with cirrhosis often exhibit cardiac autonomic dysfunction (CAD), characterized by enhanced cardiac sympathetic activity and diminished cardiac vagal tone, leading to increased morbidity and mortality. This study delineates the cellular and molecular mechanisms associated with altered neuronal activities causing cirrhosis-induced CAD. Biliary [...] Read more.
Patients with cirrhosis often exhibit cardiac autonomic dysfunction (CAD), characterized by enhanced cardiac sympathetic activity and diminished cardiac vagal tone, leading to increased morbidity and mortality. This study delineates the cellular and molecular mechanisms associated with altered neuronal activities causing cirrhosis-induced CAD. Biliary and nonbiliary cirrhotic rats were produced by common bile duct ligation (CBDL) and intraperitoneal injections of thioacetamide (TAA), respectively. Three weeks after CBDL or TAA injection, the assessment of heart rate variability revealed autonomic imbalance in cirrhotic rats. We observed increased excitability in stellate ganglion (SG) neurons and decreased excitability in intracardiac ganglion (ICG) neurons in cirrhotic rats compared to sham-operated controls. Additionally, threshold, rheobase, and action potential duration exhibited opposite alterations in SG and ICG neurons, along with changes in afterhyperpolarization duration. A- and M-type K⁺ channels were significantly downregulated in SG neurons, while M-type K⁺ channels were upregulated, with downregulation of the N- and L-type Ca2⁺ channels in the ICG neurons of cirrhotic rats, both in transcript expression and functional activity. Collectively, these findings suggest that cirrhosis induces an imbalance between cardiac sympathetic and parasympathetic neuronal activities via the differential regulation of K+ and Ca2+ channels. Thus, cirrhosis-induced CAD may be associated with impaired autonomic efferent functions within the homeostatic reflex arc that regulates cardiac functions. Full article
(This article belongs to the Special Issue Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets)
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9 pages, 221 KiB  
Article
Impaired Modulation of the Autonomic Nervous System in Adult Patients with Major Depressive Disorder
by Elise Böttcher, Lisa Sofie Schreiber, David Wozniak, Erik Scheller, Frank M. Schmidt and Johann Otto Pelz
Biomedicines 2024, 12(6), 1268; https://doi.org/10.3390/biomedicines12061268 - 6 Jun 2024
Cited by 2 | Viewed by 1728
Abstract
Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate [...] Read more.
Patients with major depressive disorder (MDD) have an increased risk for cardiac events. This is partly attributed to a disbalance of the autonomic nervous system (ANS) indicated by a reduced vagal tone and a (relative) sympathetic hyperactivity. However, in most studies, heart rate variability (HRV) was only examined while resting. So far, it remains unclear whether the dysbalance of the ANS in patients with MDD is restricted to resting or whether it is also evident during sympathetic and parasympathetic activation. The aim of this study was to compare the responses of the ANS to challenges that stimulated the sympathetic and, respectively, the parasympathetic nervous systems in patients with MDD. Forty-six patients with MDD (female 27 (58.7%), mean age 44 ± 17 years) and 46 healthy controls (female 26 (56.5%), mean age 44 ± 20 years) underwent measurement of time- and frequency-dependent domains of HRV at rest, while standing (sympathetic challenge), and during slow-paced breathing (SPB, vagal, i.e., parasympathetic challenge). Patients with MDD showed a higher heart rate, a reduced HRV, and a diminished vagal tone during resting, standing, and SPB compared to controls. Patients with MDD and controls responded similarly to sympathetic and vagal activation. However, the extent of modulation of the ANS was impaired in patients with MDD, who showed a reduced decrease in the vagal tone but also a reduced increase in sympathetic activity when switching from resting to standing. Assessing changes in the ANS during sympathetic and vagal activation via respective challenges might serve as a future biomarker and help to allocate patients with MDD to therapies like HRV biofeedback and psychotherapy that were recently found to modulate the vagal tone. Full article
(This article belongs to the Special Issue Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets)
13 pages, 1659 KiB  
Article
Cardiovascular Autonomic Dysfunction in Hospitalized Patients with a Bacterial Infection: A Longitudinal Observational Pilot Study in the UK
by Monica Arias-Colinas, Alfredo Gea, Joseph Kwan, Michael Vassallo, Stephen C. Allen and Ahmed Khattab
Biomedicines 2024, 12(6), 1219; https://doi.org/10.3390/biomedicines12061219 - 30 May 2024
Viewed by 1278
Abstract
Purpose: A temporal reduction in the cardiovascular autonomic responses predisposes patients to cardiovascular instability after a viral infection and therefore increases the risk of associated complications. These findings have not been replicated in a bacterial infection. This pilot study will explore the prevalence [...] Read more.
Purpose: A temporal reduction in the cardiovascular autonomic responses predisposes patients to cardiovascular instability after a viral infection and therefore increases the risk of associated complications. These findings have not been replicated in a bacterial infection. This pilot study will explore the prevalence of cardiovascular autonomic dysfunction (CAD) in hospitalized patients with a bacterial infection. Methods: A longitudinal observational pilot study was conducted. Fifty participants were included: 13 and 37 participants in the infection group and healthy group, respectively. Recruitment and data collection were carried out during a two-year period. Participants were followed up for 6 weeks: all participants’ cardiovascular function was assessed at baseline (week 1) and reassessed subsequently at week 6 so that the progression of the autonomic function could be evaluated over that period of time. The collected data were thereafter analyzed using STATA/SE version 16.1 (StataCorp). The Fisher Exact test, McNemar exact test, Mann–Whitney test and Wilcoxon test were used for data analysis. Results: 32.4% of the participants in the healthy group were males (n = 12) and 67.6% were females (n = 25). Participants’ age ranged from 33 years old to 76 years old with the majority being 40–60 years of age (62.1%) (Mean age 52.4 SD = 11.4). Heart rate variability (HRV) in response to Valsalva Maneuver, metronome breathing, standing and sustained handgrip in the infection group was lower than in the healthy group throughout the weeks. Moreover, both the HRV in response to metronome breathing and standing up showed a statistically significant difference when the mean values were compared between both groups in week 1 (p = 0.03 and p = 0.013). The prevalence of CAD was significantly higher in the infection group compared to healthy volunteers, both at the beginning of the study (p = 0.018) and at the end of follow up (p = 0.057), when all patients had been discharged. Conclusions: CAD, as assessed by the HRV, is a common finding during the recovery period of a bacterial infection, even after 6 weeks post-hospital admission. This may increase the risk of complications and cardiovascular instability. It may therefore be of value to conduct a wider scale study to further evaluate this aspect so recommendations can be made for the cardiovascular autonomic assessment of patients while they are recovering from a bacterial infectious process. Full article
(This article belongs to the Special Issue Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets)
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Review

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24 pages, 808 KiB  
Review
Chronic Stress and Headaches: The Role of the HPA Axis and Autonomic Nervous System
by Aleksandar Sic, Marko Bogicevic, Nebojsa Brezic, Clara Nemr and Nebojsa Nick Knezevic
Biomedicines 2025, 13(2), 463; https://doi.org/10.3390/biomedicines13020463 - 13 Feb 2025
Cited by 3 | Viewed by 3999
Abstract
Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased [...] Read more.
Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores the intricate relationship between stress and headaches, focusing on the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS). Persistent stress could lead to neuroinflammation, increased pain sensitivity, and vascular changes that could contribute to headache development and progression. The bidirectional nature of this relationship creates a vicious cycle, with recurrent headaches becoming a source of additional stress. Dysregulation of the HPA axis and ANS imbalance could amplify susceptibility to headaches, intensifying their frequency and severity. While pharmacological interventions remain common, non-pharmacological approaches targeting stress reduction, such as cognitive-behavioral therapy, biofeedback, and relaxation techniques, offer promising avenues for comprehensive headache management. By addressing the underlying stress-related mechanisms, these approaches provide a sustainable strategy to reduce headache frequency and improve patients’ quality of life. Full article
(This article belongs to the Special Issue Autonomic Dysfunction in Neurological Disorders: Novel Mechanisms and Targets)
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