Autonomic dysregulation

Ghrelin and its mimetics have been shown to reduce cisplatin-induced emesis in preclinical studies using ferrets and shrews. This study investigated the effectiveness of ghrelin and des-acyl ghrelin (DAG) in antagonizing cisplatin-induced emesis and physiological changes indicative of nausea in Suncus murinus. Animals implanted with radiotelemetry devices were administered ghrelin (0.2, 1.0, and 5.0 μg/day), DAG (0.2, 1.0, and 5.0 μg/day), or saline (14 μL/day) intracerebroventricularly 4 days before and 3 days after treatment with cisplatin (30 mg/kg)...

Heart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. In this review we present evidence by which changes in HRV might precede the onset of depression. We describe several pathways that can facilitate this relationship...

The autonomic nervous system (ANS) regulates involuntary bodily functions such as blood pressure, heart rate, breathing, and digestion, in addition to controlling motivation and behavior. In older adults, the ANS is dysregulated, which changes the ability of the ANS to respond to physiological signals, regulate cardiovascular autonomic functionality, diminish gastric motility, and exacerbate sleep problems. For example, a decrease in heart rate variability, or the variation in the interval between heartbeats, is one of the most well-known alterations in the ANS associated with health issues, including cardiovascular diseases and cognitive decline...

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) carries variability in arterial flow pulsatility (AFP). RESEARCH QUESTION: What changes in cerebral and somatic oxygenation, hemodynamics, and autonomic function are associated with AFP during VA-ECMO? METHODS: This is a prospective study of children on VA-ECMO undergoing neuromonitoring. AFP was quantified by arterial blood pressure pulse amplitude and subcategorized: no pulsatility (<1 mmHg), minimal pulsatility (1 to <5 mmHg), moderate pulsatility (5 to <15 mmHg) and high pulsatility (≥15 mmHg)...

BACKGROUND: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. METHODS: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells...

Overexpression of the Ube3a gene and the resulting increase in Ube3a protein are linked to autism spectrum disorder (ASD). However, the cellular and molecular processes underlying Ube3a-dependent ASD remain unclear. Using both male and female mice, we find that neurons in the somatosensory cortex of the Ube3a 2× Tg ASD mouse model display reduced dendritic spine density and increased immature filopodia density. Importantly, the increased gene dosage of Ube3a in astrocytes alone is sufficient to confer alterations in neurons as immature dendritic protrusions, as observed in primary hippocampal neuron cultures...

The development of multicellular organisms depends on spatiotemporally controlled differentiation of numerous cell types and their maintenance. To generate such diversity based on the invariant genetic information stored in DNA, epigenetic mechanisms, which are heritable changes in gene function that do not involve alterations to the underlying DNA sequence, are required to establish and maintain unique gene expression programs. Polycomb repressive complexes represent a paradigm of epigenetic regulation of developmentally regulated genes, and the roles of these complexes as well as the epigenetic marks they deposit, namely H3K27me3 and H2AK119ub, have been extensively studied...

OBJECTIVES: Small fiber neuropathy (SFN) affects the fibers involved in cutaneous and visceral pain and temperature sensation and are a crucial part of the autonomic nervous system. Autonomic dysfunction secondary to SFN and autoimmune receptor antibodies is being increasingly recognized, and gastrointestinal (GI) manifestations include constipation, early satiety, nausea, vomiting, and diarrhea. Enteric nervous system involvement may be a possible explanation of abnormal GI motility patterns seen in these patients...

UNLABELLED: Many mechanisms responsible for COVID-19 pathogenesis are well-established, but COVID-19 includes features with unclear pathogenesis, such as autonomic dysregulation, coagulopathies, and high levels of inflammation. The receptor for the SARS-CoV-2 spike protein receptor-binding domain (RBD) is angiotensin-converting enzyme 2 (ACE2). We hypothesized that some COVID-19 patients may develop antibodies that have a negative molecular image of RBD sufficiently similar to ACE2 to yield ACE2-like catalytic activity-ACE2-like abzymes...

Postpartum depression (PPD) is a serious mental health issue among women after childbirth, and screening systems that incorporate questionnaires have been utilized to screen for PPD. These questionnaires are sensitive but less specific, and the additional use of objective measures could be helpful. The present study aimed to verify the usefulness of a measure of autonomic function, heart rate variability (HRV), which has been reported to be dysregulated in people with depression. Among 935 women who had experienced childbirth and completed the Edinburgh Postnatal Depression Scale (EPDS), HRV was measured in EPDS-positive women ( n = 45) 1 to 4 weeks after childbirth using a wearable device...

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain...

Poor neurodevelopment is often observed with congenital heart disease (CHD), especially with mutations in chromatin modifiers. Here analysis of mice with hypoplastic left heart syndrome (HLHS) arising from mutations in Sin3A associated chromatin modifier Sap130 , and adhesion protein Pcdha9, revealed neurodevelopmental and neurobehavioral deficits reminiscent of those in HLHS patients. Microcephaly was associated with impaired cortical neurogenesis, mitotic block, and increased apoptosis. Transcriptional profiling indicated dysregulated neurogenesis by REST, altered CREB signaling regulating memory and synaptic plasticity, and impaired neurovascular coupling modulating cerebral blood flow...

INTRODUCTION AND IMPORTANCE: Multiple sclerosis is known to be associated with both sympathetic and parasympathetic cardiovascular autonomic dysregulation. Thus, patients with multiple sclerosis comorbidity represent a potentially challenging patient population in cardiac surgery, especially in on-pump operations. Despite this, very little is known about the hemodynamics during cardiopulmonary bypass and the optimal perfusion strategy for patients with multiple sclerosis undergoing cardiac operations...

Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer's disease (AD). Gaining insight into the molecular mechanisms underlying this vulnerability will help reveal genes and pathways at play during incipient stages of the disease. Here, we use a data-driven functional genomics approach to model ECII neurons in silico and identify the proto-oncogene DEK as a regulator of tau pathology. We show that epigenetic changes caused by Dek silencing alter activity-induced transcription, with major effects on neuronal excitability...

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopment disorder that affects approximately 5% of the population. The disorder is characterized by impulsivity, hyperactivity, and deficits in attention and cognition, although symptoms vary across patients due to the heterogenous and polygenic nature of the disorder. Stimulant medications are the standard of care treatment for ADHD patients, and their effectiveness has led to the dopaminergic hypothesis of ADHD in which deficits in dopaminergic signaling, especially in cortical brain regions, mechanistically underly ADHD pathophysiology...

OBJECTIVE: Enalapril has shown satisfactory potential in controlling increased and sustained blood pressure (BP). However, multiple dysregulated mechanisms that interact with each other and are involved in the pathophysiology of arterial hypertension may not be affected, contributing to the remaining cardiovascular risk. Using an exercise training protocol, we investigated whether adding both approaches to arterial hypertension management could promote higher modulation of regulatory mechanisms of BP in postmenopausal rats...

Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role...

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...

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. Psychosocial well-being is affected. Previously, we assessed burden of disease for Myasthenia gravis (MG). Here, we aim to elucidate burden of disease by comparing health-related quality of life (HRQoL) of patients with LEMS to the general population (genP) as well as MG patients. METHODS: A questionnaire-based survey included sociodemographic and clinical data along with standardized questionnaires, e...

Several neurochemical systems converge in the prefrontal cortex (PFC) to regulate cognitive and motivated behaviors. A rich network of endogenous opioid peptides and receptors spans multiple PFC cell types and circuits, and this extensive opioid system has emerged as a key substrate underlying reward, motivation, affective behaviors, and adaptations to stress. Here, we review the current evidence for dysregulated cortical opioid signaling in the pathogenesis of psychiatric disorders. We begin by providing an introduction to the basic anatomy and function of the cortical opioid system, followed by a discussion of endogenous and exogenous opioid modulation of PFC function at the behavioral, cellular, and synaptic level...