Search Results (67)

The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11β-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11β-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated Aδ-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (>70 µm). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies. Full article

Background: Borderline personality disorder (BPD) is a severe psychiatric condition characterised by emotional instability, impulsivity, interpersonal dysfunction, and self-injurious behaviours. Despite growing clinical interest, the neuropsychological mechanisms underlying these symptoms are still not fully understood. This review aims to summarise findings from neuroimaging, psychophysiological, and neurodevelopmental studies in order to clarify the neurobiological and physiological basis of BPD, with a particular focus on emotional dysregulation and implications for the treatment of adolescents. Methods: A narrative review was conducted, integrating results from longitudinal neurodevelopmental studies, functional and structural neuroimaging research (e.g. FMRI and PET), and psychophysiological assessments (e.g., heart rate variability and cortisol reactivity). Studies were selected based on their contribution to understanding the neural correlates of BPD symptom dimensions, particularly emotion dysregulation, impulsivity, interpersonal dysfunction, and self-harm. Results: Findings suggest that early reductions in amygdala volume, as early as age 13 predict later BPD symptoms. Hyperactivity of the amygdala, combined with hypoactivity in the prefrontal cortex, underlies deficits in emotion regulation. Orbitofrontal abnormalities correlate with impulsivity, while disruptions in the default mode network and oxytocin signaling are related to interpersonal dysfunction. Self-injurious behaviour appears to serve a neuropsychological function in regulating emotional pain and trauma-related arousal. This is linked to disruption of the hypothalamic-pituitary-adrenal (HPA) axis and structural brain alterations. The Unified Protocol for Adolescents (UP-A) was more effective to Mentalization-Based Therapy for Adolescents (MBT-A) at reducing emotional dysregulation compared, though challenges in treating identity disturbance and relational difficulties remain. Discussion: The reviewed evidence suggests that BPD has its in early neurodevelopmental vulnerability and is sustained by maladaptive neurophysiological processes. Emotional dysregulation emerges as a central transdiagnostic mechanism. Self-harm may serve as a strategy for regulating emotions in response to trauma-related neural dysregulation. These findings advocate for the integration of neuroscience into psychotherapeutic practice, including the application of neuromodulation techniques and psychophysiological monitoring. Conclusions: A comprehensive understanding of BPD requires a neuropsychologically informed framework. Personalised treatment approaches combining pharmacotherapy, brain-based interventions, and developmentally adapted psychotherapies—particularly DBT, psychodynamic therapy, and trauma-informed care—are essential. Future research should prioritise interdisciplinary, longitudinal studies to further bridge the gap between neurobiological findings and clinical innovation. Full article

Various cardiac pathologies such as ischemic/non-ischemic heart disease, valvular heart disease and genetic heart disease may impair cardiac function and lead to heart failure (HF). Each individual condition but also the common endpoint of HF may involve the brain and the immune system next to the heart. The interaction of these systems plays an important role, particularly in the pathogenesis and prognosis of HF, and stress plays a pivotal role in this interaction. The stress system (SS) of the body can be activated by any stress factor exceeding a predefined threshold and all body structures including brain, heart and immune system can be affected. The SS is also responsible for body homeostasis. Both acute and chronic stress may lead to the development of acute and chronic heart disease. Magnetic Resonance Imaging (MRI) is the ideal noninvasive tool without radiation that can provide valuable information about the effect of the SS in various systems/organs using targeted protocols. A holistic approach provided by MRI has the potential to improve our knowledge regarding stress mechanisms on the axis of heart–brain–immune system in HF that may impact effective, individualized treatment. In this review paper, we describe how MRI can be used as a noninvasive tool to assess the effect of stress on the brain–immune system-heart-axis, discussing current possibilities, limitations and future directions. Full article

Coronary artery disease (CAD) and mental health disorders, particularly depression and anxiety, exhibit a complex, bidirectional relationship that adversely influences clinical outcomes and mortality. Mental illnesses account for approximately 8 million deaths annually, while cardiovascular diseases, including CAD, contribute to about 17 million deaths, with CAD alone responsible for one-third of deaths among individuals aged ≥35 years. This review offers a structured synthesis of current knowledge focusing on the (1) epidemiology, emphasizing the reciprocal risk between CAD and psychiatric conditions; (2) pathophysiological insights, including inflammation, neurohormonal dysregulation, platelet hyperactivation, and shared genetic determinants; and (3) therapeutic approaches, encompassing pharmacological management, psychotherapeutic interventions, and integrated care models. Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacologic agents of choice in patients with CAD and depression due to their favorable cardiac profile, while cognitive behavioral therapy (CBT) offers psychological benefit. However, evidence for mortality reduction remains limited. Emerging research highlights the importance of biomarker-driven care, gut–brain–heart axis modulation, and AI-enabled clinical integration. Full article

Shelter environments can be inherently stressful for dogs, a highly social species that forms strong attachment bond with humans. This study evaluated stress responses in 26 shelter dogs during routine veterinary examinations, analyzing behavioral scores alongside physiological and hormonal parameters, including heart rate, body temperature, cortisol (CRT), oxytocin (OXT), serotonin (5-HT), tryptophan (TRP), and interleukin-6 (IL-6). A significant negative correlation was observed between OXT and CRT (ρ = –0.540, p = 0.007), particularly in dogs exhibiting relaxed behavior. OXT was also negatively correlated with body temperature (ρ = –0.435, p = 0.034), supporting its potential role in modulating stress-induced hyperthermia. No significant associations were found between TRP, 5-HT, IL-6, or other physiological measures and behavioral scores. The absence of correlation between TRP and 5-HT may be due to blood–brain barrier regulation, while IL-6′s lack of association suggests further investigation is needed to clarify its role in canine stress responses. These findings highlight OXT’s possible buffering effect on the hypothalamic–pituitary–adrenal axis and suggest that behavioral assessment may offer a more sensitive measure of canine stress than hormonal or physiological parameters alone. Future studies with larger and more diverse samples are needed to confirm and expand upon these results. Full article

(1) Background: Heart failure (HF) and dementia are commonly associated with the elderly. A significant percentage of patients with HF are at high risk of cognitive decline and progression to dementia. Cognitive impairment is associated with both diseases. However, the molecules and mechanisms that affect the HF–dementia axis are poorly understood. (2) Objective: In this work, we aim to identify potential proteins that modulate HF and dementia. (3) Methods: We applied a pipeline using bioinformatic tools that robustly perform a literature search. (4) Results: Our results show that apolipoprotein E (APOE), c-reactive protein (CRP), interleukin 6 (IL6), renin (REN), and angiotensin-converting enzyme (ACE) proteins are important for maintaining homeostasis in the heart–brain axis. Additionally, deregulated levels of these proteins are associated with neuronal and cardiovascular diseases. (5) Conclusions: Our work highlights proteins that may help in understanding the pathophysiological relationship between HF and dementia. Moreover, these proteins may also be potential biomarkers and/or therapeutic targets. Full article

The intricate brain–heart interaction, essential for physiological balance, is largely governed by the autonomic nervous system (ANS). This bidirectional communication, involving both the sympathetic and parasympathetic branches of the ANS, is critical for maintaining cardiac homeostasis. Dysregulation of the ANS is a significant factor in cardiovascular diseases. Beyond the ANS, higher brain functions, particularly through interoceptive prediction, contribute to this dynamic interplay. The Cav1.3 L-type calcium channel, expressed in both the central nervous system (CNS) and the heart, is crucial for this interaction. Cav1.3, a key regulator of cellular excitability, exhibits genetic variations that are linked to both neurological and cardiac disorders, highlighting its pivotal role in the brain–heart axis. This review aims to delve into the under-explored role of Cav1.3 in brain–heart interaction, specifically examining how it modulates ANS activity and, consequently, the cardiac function. This will illuminate its significant role in the broader context of brain–heart interactions. Full article

In this review article, we discuss and explore the role of bacteria-derived hydrogen sulfide. Hydrogen sulfide is a signaling molecule produced endogenously that plays an important role in health and disease. It is also produced by the gut microbiome. In the setting of microbial disturbances leading to disruption of intestinal homeostasis (dysbiosis), the concentration of available hydrogen sulfide can also vary leading to pathologic sequelae. The brain–gut axis is the original studied paradigm of gut microbiome and host interaction. In recent years, our understanding of microbial and host interaction has expanded greatly to include specific pathways that have branched into their own axes. These axes share a principal concept of microbiota changes, intestinal permeability, and an inflammatory response, some of which are modulated by hydrogen sulfide (H₂S). In this review, we will discuss multiple axes including the gut–immune, gut–heart, and gut–endocrine axes. We will evaluate the role of H₂S in modulation of intestinal barrier, mucosal healing in intestinal inflammation and tumor genesis. We will also explore the role of H₂S in alpha-synuclein aggregation and ischemic injury. Finally, we will discuss H₂S in the setting of metabolic syndrome as int pertains to hypertension, atherosclerosis and glucose-like peptide-1 activity. Majority of studies that evaluate hydrogen sulfide focus on endogenous production; the role of this review is to examine the lesser-known bacteria-derived source of hydrogen sulfide in the progression of diseases as it relates to these axes. Full article

With an aging population, the incidence of both ischemic heart disease and strokes have become the most prevalent diseases globally. These diseases have similar risk factors, such as hypertension, diabetes, and smoking. However, there is also evidence of a relationship between the heart and the brain, referred to as the heart–brain axis. In this relationship, dysfunction of either organs can lead to injury to the other. There are several proposed physiologies to explain this relationship. These theories usually involve vascular, neuromodulatory, and inflammatory processes; however, few articles have explored and compared these different mechanisms of interaction between the heart and brain. A better understanding of the heart–brain axis can inform physicians of current and future treatment and preventive care options in heart and brain pathologies. The relationship between the brain and heart depends on inflammation, vascular anatomy and function, and neuromodulation. The pathways connecting these organs often become injured or dysfunctional when a major pathology, such as a myocardial infarction or stroke, occurs. This leads to long-term impacts on the patient’s overall health and risk for future disease. This study summarizes the current research involved in the heart–brain axis, relates these interactions to different diseases, and proposes future research in the field of neurocardiology. Conditions of the brain and heart are some of the most prevalent diseases. Through understanding the connection between these two organs, we can help inform patients and physicians of novel therapeutics for these pathologies. Full article

Emerging evidence underscores the pivotal role of the gut microbiota in regulating emotional and behavioral responses via the microbiota–gut–brain axis. This study explores associations between pediatric obstructive sleep apnea (OSA), emotional distress (ED), and gut microbiome alterations before and after OSA treatment. Sixty-six children diagnosed with OSA via polysomnography participated, undergoing adenotonsillectomy alongside routine educational sessions. ED was assessed using the OSA-18 questionnaire, categorizing participants into high ED (scores ≥ 11, 52%) and low ED (scores < 11, 48%) groups. Gut microbiome analysis revealed significant diversity differences, with high ED linked to a reduced Shannon index (p = 0.03) and increased beta diversity (p = 0.01). Three months post-treatment, significant improvements were observed in OSA symptoms, ED scores, and gut microbiome alpha diversity metrics among 55 participants (all p < 0.04). Moreover, changes in the relative abundances of Veillonella, Bifidobacterium, Flavonifractor, and Agathobacter, as well as ultra-low frequency power and low frequency power of sleep heart rate variability, were independently associated with ED score alterations. These findings underscore the gut microbiome’s critical role in the emotional and behavioral symptoms associated with pediatric OSA, suggesting that microbiome-targeted interventions could complement traditional treatments for ED reduction and emphasizing the need for further research. Full article

The problem of marine noise pollution has a long history. Strong noise (>120 dB re 1 µPa) will affects the growth, development, physiological responses, and behaviors of fish, and also can induce the stress response, posing a mortal threat. Although many studies have reported that underwater noise may affect the survival of fish by disturbing their nervous system and endocrine system, the underlying causes of death due to noise stimulation remain unknown. Therefore, in this study, we used the underwater noise stress models to conduct underwater strong noise (50–125 dB re 1 µPa, 10–22,000 Hz) stress experiments on small yellow croaker for 10 min (short-term noise stress) and 6 days (long-term noise stress). A total of 150 fishes (body weight: 40–60 g; body length: 12–14 cm) were used in this study. Omics (metabolomics and transcriptomics) studies and quantitative analyses of important genes (HPA (hypothalamic–pituitary–adrenal)-axis functional genes) were performed to reveal genetic and metabolic changes in the important tissues associated with the HPA axis (brain, heart, and adrenal gland). Finally, we found that the strong noise pollution can significantly interfere with the expression of HPA-axis functional genes (including corticotropin releasing hormone (CRH), corticotropin releasing hormone receptor 2 (CRHR2), and arginine vasotocin (AVT)), and long-term stimulation can further induce metabolic disorders of the functional tissues (brain, heart, and adrenal gland), posing a lethal threat. Meanwhile, we also found that there were two kinds of death processes, direct death and chronic death, and both were closely related to the duration of stimulation and the regulation of the HPA axis. Full article

Within the central nervous system, synaptic plasticity, fundamental to processes like learning and memory, is largely driven by activity-dependent changes in synaptic strength. This plasticity often manifests as long-term potentiation (LTP) and long-term depression (LTD), which are bidirectional modulations of synaptic efficacy. Strong epidemiological and experimental evidence show that the heart–brain axis could be severely compromised by both neurological and cardiovascular disorders. Particularly, cardiovascular disorders, such as heart failure, hypertension, obesity, diabetes and insulin resistance, and arrhythmias, may lead to cognitive impairment, a condition known as cardiogenic dementia. Herein, we review the available knowledge on the synaptic and molecular mechanisms by which cardiogenic dementia may arise and describe how LTP and/or LTD induction and maintenance may be compromised in the CA1 region of the hippocampus by heart failure, metabolic syndrome, and arrhythmias. We also discuss the emerging evidence that endothelial dysfunction may contribute to directly altering hippocampal LTP by impairing the synaptically induced activation of the endothelial nitric oxide synthase. A better understanding of how CV disorders impact on the proper function of central synapses will shed novel light on the molecular underpinnings of cardiogenic dementia, thereby providing a new perspective for more specific pharmacological treatments. Full article

Sleep-disordered breathing (SDB), which includes conditions such as obstructive sleep apnea (OSA) and central sleep apnea (CSA), is an independent risk factor for cerebral small vessel disease (CSVD), stroke, heart failure, arrhythmias, and other cardiovascular disorders. The influence of OSA on brain structure and cognitive function has become an essential focus in the heart-brain axis, given its potential role in developing neurocognitive abnormalities. In this review, we found that OSA plays a significant role in the cardio-neural pathway that leads to the development of cerebral small vessel disease and neurocognitive decline. Although data is still limited on this topic, understanding the critical role of OSA in the heart-brain axis could lead to the utilization of imaging modalities to simultaneously identify early signs of pathology in both organ systems based on the known OSA-driven pathological pathways that result in a disease state in both the cardiovascular and cerebrovascular systems. This narrative review aims to summarize the current link between OSA and neurocognitive disorders, cardio-neural pathophysiology, and the treatment options available for patients with OSA-related neurocognitive disorders. Full article

Arrhythmias and depression are recognized as diseases of the heart and brain, respectively, and both are major health threats that often co-occur with a bidirectional causal relationship. The autonomic nervous system (ANS) serves as a crucial component of the heart–brain axis (HBA) and the pathway of interoception. Cardiac activity can influence emotional states through ascending interoceptive pathways, while psychological stress can precipitate arrhythmias via the ANS. However, the HBA and interoception frameworks are often considered overly broad, and the precise mechanisms underlying the bidirectional relationship between depression and arrhythmias remain unclear. This narrative review aims to synthesize the existing literature, focusing on the pathological mechanisms of the ANS in depression and arrhythmia while integrating other potential mechanisms to detail heart–brain interactions. In the bidirectional communication between the heart and brain, we emphasize considering various internal factors such as genes, personality traits, stress, the endocrine system, inflammation, 5-hydroxytryptamine, and behavioral factors. Current research employs multidisciplinary knowledge to elucidate heart–brain relationships, and a deeper understanding of these interactions can help optimize clinical treatment strategies. From a broader perspective, this study emphasizes the importance of considering the body as a complex, interconnected system rather than treating organs in isolation. Investigating heart–brain interactions enhance our understanding of disease pathogenesis and advances medical science, ultimately improving human quality of life. Full article

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin–heart axis, focusing on insulin’s multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin–angiotensin–aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin–heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes. Full article