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Abstract The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.

The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area. [ABSTRACT FROM AUTHOR]

Abstract Background Suicide is a leading cause of death globally. Identifying individuals at higher suicidal risk is a key to suicide prevention. Patients with comorbid psychiatric disorders, especially major depressive disorder (MDD), are known to be highly prone to suicidality. However, the behavioural manifestations of MDD and suicidality are distinct, indicating potentially unique molecular underpinnings, of which our current understanding is limited. Delineating the unique and shared molecular etiologies of MDD and suicidality would be imperative to devise effective treatment strategies for suicidal behaviour. To this end, we analysed the existing literature pertaining to transcriptomic alterations in brain samples of individuals who died from MDD or by suicide. Subsequently, biological processes associated with the differentially expressed genes (DEGs) were identified. In addition, we also examined the transcriptional regulators (TRs) potentially driving cortical gene expression changes in MDD and suicidality. Results A set of immunological genes was found to be commonly upregulated in MDD but downregulated in suicide. Actin and cytoskeleton organization genes also had a similar trend. In addition, MDD-upregulated and suicide-downregulated genes were found to have overrepresented target sites for 40 TRs associated with epigenetic as well as polymerase-mediated regulation. Any variations in the levels of these TRs could be of behavioural consequence in MDD and suicidality. Conclusions A clear understanding of the condition-specific neurotranscriptomic differences in MDD and suicidality would be valuable in order to delineate the biological mechanisms underlying these conditions. Importantly, it would provide insights into more effective treatment strategies for suicidality among individuals with or without MDD. However, we have yet to determine the molecular basis of suicidality in the context of MDD and as a standalone mental condition. In this regard, the present findings would be of scientific and clinical relevance and could stimulate further research.

Background: Suicide is a leading cause of death globally. Identifying individuals at higher suicidal risk is a key to suicide prevention. Patients with comorbid psychiatric disorders, especially major depressive disorder (MDD), are known to be highly prone to suicidality. However, the behavioural manifestations of MDD and suicidality are distinct, indicating potentially unique molecular underpinnings, of which our current understanding is limited. Delineating the unique and shared molecular etiologies of MDD and suicidality would be imperative to devise effective treatment strategies for suicidal behaviour. To this end, we analysed the existing literature pertaining to transcriptomic alterations in brain samples of individuals who died from MDD or by suicide. Subsequently, biological processes associated with the differentially expressed genes (DEGs) were identified. In addition, we also examined the transcriptional regulators (TRs) potentially driving cortical gene expression changes in MDD and suicidality. Results: A set of immunological genes was found to be commonly upregulated in MDD but downregulated in suicide. Actin and cytoskeleton organization genes also had a similar trend. In addition, MDD-upregulated and suicide-downregulated genes were found to have overrepresented target sites for 40 TRs associated with epigenetic as well as polymerase-mediated regulation. Any variations in the levels of these TRs could be of behavioural consequence in MDD and suicidality. Conclusions: A clear understanding of the condition-specific neurotranscriptomic differences in MDD and suicidality would be valuable in order to delineate the biological mechanisms underlying these conditions. Importantly, it would provide insights into more effective treatment strategies for suicidality among individuals with or without MDD. However, we have yet to determine the molecular basis of suicidality in the context of MDD and as a standalone mental condition. In this regard, the present findings would be of scientific and clinical relevance and could stimulate further research. [ABSTRACT FROM AUTHOR]

The neuroimmune system is a collection of immune cells, cytokines, and the glymphatic system that plays a pivotal role in the pathogenesis and progression of Alzheimer's disease (AD). Of particular focus are cytokines, a group of immune signaling molecules that facilitate communication among immune cells and contribute to inflammation in AD. Extensive research has shown that the dysregulated secretion of certain cytokines (IL-1β, IL-17, IL-12, IL-23, IL-6, and TNF-α) promotes neuroinflammation and exacerbates neuronal damage in AD. However, anti-inflammatory cytokines (IL-2, IL-3, IL-33, and IL-35) are also secreted during AD onset and progression, thereby preventing neuroinflammation. This review summarizes the involvement of pro- and anti-inflammatory cytokines in AD pathology and discusses their therapeutic potential. [ABSTRACT FROM AUTHOR]

Abstract Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain’s resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Heavy ethanol consumption during adolescence has been linked to neuroimmune response dysregulation and cognitive deficits in the developing adolescent brain. During adolescence, the brain is particularly susceptible to the pharmacological effects of ethanol that are induced by acute and chronic bouts of exposure. Numerous preclinical rodent model studies have used different ethanol administration techniques, such as intragastric gavage, self-administration, vapor, intraperitoneal, and free access, and while most models indicated proinflammatory neuroimmune responses in the adolescent brain, there are various factors that appear to influence this observation. This review synthesizes the most recent findings of the effects of adolescent alcohol use on toll-like receptors, cytokines, and chemokines, as well as the activation of astrocytes and microglia with an emphasis on differences associated with the duration of ethanol exposure (acute vs. chronic), the amount of exposure (e.g., dose or blood ethanol concentrations), sex differences, and the timing of the neuroimmune observation (immediate vs. persistent). Finally, this review discusses new therapeutics and interventions that may ameliorate the dysregulation of neuroimmune maladaptations after ethanol exposure. [ABSTRACT FROM AUTHOR]

Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges. Differences in coping may involve differences in resilience and vulnerability and/or whether the stressful context allows adaptive learning and responses. We provide data demonstrating both common (corticosterone, SIH and fear behaviors) and distinguishing (sleep and neuroimmune) responses that are associated with an individual's ability to respond and relative resilience and vulnerability. We discuss neurocircuitry regulating integrated stress, sleep, neuroimmune and fear responses, and show that responses can be modulated at the neural level. Finally, we discuss factors that need to be considered in models of integrated stress responses and their relevance for understanding stress-related disorders in humans.

Heavy ethanol consumption during adolescence has been linked to neuroimmune response dysregulation and cognitive deficits in the developing adolescent brain. During adolescence, the brain is particularly susceptible to the pharmacological effects of ethanol that are induced by acute and chronic bouts of exposure. Numerous preclinical rodent model studies have used different ethanol administration techniques, such as intragastric gavage, self-administration, vapor, intraperitoneal, and free access, and while most models indicated proinflammatory neuroimmune responses in the adolescent brain, there are various factors that appear to influence this observation. This review synthesizes the most recent findings of the effects of adolescent alcohol use on toll-like receptors, cytokines, and chemokines, as well as the activation of astrocytes and microglia with an emphasis on differences associated with the duration of ethanol exposure (acute vs. chronic), the amount of exposure (e.g., dose or blood ethanol concentrations), sex differences, and the timing of the neuroimmune observation (immediate vs. persistent). Finally, this review discusses new therapeutics and interventions that may ameliorate the dysregulation of neuroimmune maladaptations after ethanol exposure.

Introduction Exposure to alcohol causes imbalances in neuroimmune function and impaired brain development. Objectives Alcohol activates neuroimmune molecules, expressed and secreted by glial cells in the brain, alter neuronal function and stimulate alcoholic behavior. Methods The study involved women aged 25-41 years-did not drink alcohol 1 month before and during pregnancy – 1-st group; women with I-II degree of alcoholism 3-13 years – 2-nd group. Embryonic material were obtained 8-15 weeks of igestation. 2-nd group were divided into subgroups. Group Alcohol (A)-alcoholic women,s embrious, included 2 subgroups: A1-embryos 8-9 weeks, A2-10-11 weeks of gestation (n=12). The Control group (K) includ control samples K1-8–9, K2-10-11 weeks (n=14). The analysis of changes in morphometric parameters was used to identify quantitative changes among glioblasts, correlation between the degree of differentiation components and the degree of influence of alcohol. For this, the program AxioVision 4.8 was used Parameters of GABAA/benzodiazepine receptors were studied by the radio-receptor assay of [3H]-flunitrazepam with synaptoneurosomes. Results Changes in glioblasts tof human brain embryos and fetuses were revealed under conditions of chronic prenatal alcoholization with an increase in gestational age compared to the control subgroups: a significant increase in the average number of glioblasts, the length of the perimeters of the presynaptic terminal, postsynaptic density, presynaptic terminal areas were significantly less (p

Objectives: The research in question aims to highlight the role of mobilizing the neuroimmune system through specific neurodynamic techniques in treating the symptomatology given by lumbosciatics. Methods: In this study I chose 14 patients, divided into two groups of 7. Group 1 being the experimental one that benefited from neurodynamic exercises and group 2 being the control one, which benefited only from classical physical therapy. Results: The experimental group showed better results in terms of pain relief than the control group after the tests performed. Conclusions: Following the research carried out on the two groups of patients diagnosed with the symptomatology of lumbosciatics, we can confirm the hypothesis from which we started and we can also find that this study concisely presented the use of neurodynamic techniques in the treatment of lumbosciatics. [ABSTRACT FROM AUTHOR]

Psoriasis is a complex immune-mediated inflammatory disorder that generates enormous interest within the scientific communities worldwide, with new therapeutic targets being constantly identified and tested. Despite the numerous topical and systemic medications available for the treatment of psoriasis, alternative therapies are still needed for the optimal management of some patients who present with localized, resistant lesions. Novel insights into the contribution of cutaneous neurogenic inflammation in the pathogenesis of psoriasis have yielded exciting new potential roles of nerve-targeting treatments, namely botulinum toxin type A (BoNT-A), for the management of this disease. This paper aims to review the existing literature on knowledge regarding the potential role of BoNT-A in psoriasis treatment, with a focus on its ability to interfere with the immunopathogenetic aspects of psoriatic disease. Furthermore, in our paper, we are also including the first report of psoriatic lesions remission following local BoNT-A injections that were administered for treating upper limb spasticity, in a patient that concomitantly suffered from psoriasis and post-stroke spasticity.

This review highlights the microbiota gut-brain axis and neurodegenerative diseases excluding studies on animal models. Gut microbiota is capable of modulating some brain activities via the microbiota gut-brain axis. A bidirectional communication exists between the gastrointestinal (GI) tract and the central nervous system (CNS) in the microbiota gut-brain axis. Gut dysbiosis has been linked to neurodegenerative diseases as a result of the imbalance in the composition of its microbiota, which has a damaging effect on the host’s health. The association between the role and mechanism of CNS disease and gut microbial is yet to be fully explored. Although some studies have shown a positive relationship between a rich diverse microbial community and the brain of the host, and a negative relationship between microbial dysbiosis, intestinal infection and human brain health, our knowledge, however, is limited due to the inability to identify the major players in this heterogeneous microbial community.

• BTX-B suppresses the progression of psoriasis-like dermatitis in IMQ-treated mice. • BTX-B suppressed the type 17 inflammation in IMQ-treated skin lesions. • BTX-B regulates psoriasis via neuroimmune system. • Neuropeptide inhibitor, including BTX can be applied to the treatment of psoriasis. Psoriasis is a multifactorial disease arises from a complex interaction of genetics, immune system, and environmental aspects. IL-23/Th17 immune axis has been considered as a primary modulator in psoriasis. In addition, several findings imply that nervous system may take a part in the pathogenesis of psoriasis, suggesting that nervous system, through its neuropeptide, may interact with immune system and lead to the formation of psoriasis. We aimed to ascertain the role of neuropeptides secreted from neurons in the pathogenesis of psoriasis in vivo. The release of neuropeptide was inhibited by injecting Botulinum toxin B (BTX-B) on Imiquimod (IMQ)-induced psoriasis-like dermatitis mice model. Quantification of skin dermatitis, infiltrating inflammatory cells, and the production of cytokines at the lesional skin area were performed by PSI score, immunostaining, and real-time PCR. We also tested the effect of selective CGRP antagonist (CGRP 8−37) on psoriasis-like dermatitis in IMQ-treated mice. BTX-B injection significantly suppressed PSI score and reduced the number of CD4+ T cells, CD11c+ dendritic cells, and the production of IL-17A/F in the lesional skin. The expressions of PGP9.5+ nerve fibers and neuropeptides (SP, CGRP) were also significantly reduced following BTX-B injection. Additionally, CGRP antagonist also suppressed the development of IMQ-induced psoriasis-like dermatitis in mice. The suppression of neuropeptide secretion in the skin by BTX injection might inhibit nerve elongation, the infiltration of immune cells, as well as IL-17 production, resulting in the improvement of psoriasis. Neuropeptide inhibitor could also be applied to the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

It is well established that adverse childhood experiences (ACEs) contribute to the development of mental disorders in adulthood. However, less is known about how childhood trauma impacts the mind and the body, whether the resulting mental disorders have different characteristics than those occurring without these antecedent conditions, and if treatment modalities need to reflect the unique nature of mental disorders rooted in trauma. Survey and biomarker data were gathered from a sample of college students (n = 93) to explore the relationship between childhood trauma and mental health. We examine how neuroimmune systems (inflammation and neuroplasticity) relate to depression and anxiety and whether these associations vary for those with and without a history of childhood trauma. Findings reveal that students with 4 or more ACEs are more likely to have depression and anxiety than students without these experiences. In addition, we find that inflammation (CRP) and neuronal health (BDNF) are associated with mental health disorders among students with four or more ACEs, but not for students without this history. These findings suggest that mental disorders associated with four or more ACEs may be uniquely tied to physiological processes, and consequently, warrant tailored treatments. The implications for mental health intervention include, 1) screening for childhood trauma, inflammation, and neuronal health and 2) referral to treatments which are theoretically and empirically tied to the root causes of mental disorders rather than those designed merely to suppress their symptoms. [ABSTRACT FROM AUTHOR]

Burn injury pain is a significant public health problem. Burn injury treatment has improved tremendously in recent decades. However, an unintended consequence is that a larger number of patients now survive more severe injuries, and face intense pain that is very hard to treat. Although many efforts have been made to find alternative treatments, opioids remain the most effective medication available. Burn patients are frequently prescribed opioids in doses and durations that are significantly higher and longer than standard analgesic dosing guidelines. Despite this, many continue to experience unrelieved pain. They are also placed at a higher risk for developing dependence and opioid use disorder. Burn injury profoundly alters the functional state of the immune system. It also alters the expression levels of receptor, effector, and signaling molecules within the spinal cord's dorsal horn. These alterations could explain the reduced potency of opioids. However, recent studies demonstrate that different opioids signal preferentially via differential signaling pathways. This ligand-specific signaling by different opioids implies that burn injury may reduce the antinociceptive potency of opioids to different degrees, in a drug-specific manner. Indeed, recent findings hint at drug-specific differences in the ability of opioids to manage burn pain early after injury, as well as differences in their ability to prevent or treat the development of chronic and neuropathic pain. Here we review the current state of opioid treatment, as well as new findings that could potentially lead to opioid-based pain management strategies that may be significantly more effective than the current solutions. [ABSTRACT FROM AUTHOR]

This review highlights the microbiota gut-brain axis and neurodegenerative diseases excluding studies on animal models. Gut microbiota is capable of modulating some brain activities via the microbiota gut-brain axis. A bidirectional communication exists between the gastrointestinal (GI) tract and the central nervous system (CNS) in the microbiota gut-brain axis. Gut dysbiosis has been linked to neurodegenerative diseases as a result of the imbalance in the composition of its microbiota, which has a damaging effect on the host’s health. The association between the role and mechanism of CNS disease and gut microbial is yet to be fully explored. Although some studies have shown a positive relationship between a rich diverse microbial community and the brain of the host, and a negative relationship between microbial dysbiosis, intestinal infection and human brain health, our knowledge, however, is limited due to the inability to identify the major players in this heterogeneous microbial community. [ABSTRACT FROM AUTHOR]

Approximately 3% of the world population suffers from depression, which is one of the most common form of mental disorder. Recent findings suggest that an interaction between the nervous system and immune system might be behind the pathophysiology of various neurological and psychiatric disorders, including depression. Neuropeptides have been shown to play a major role in mediating response to stress and inducing immune activation or suppression. Corticotropin releasing factor (CRF) is a major regulator of the hypothalamic pituitary adrenal (HPA) axis response. CRF is a stress-related neuropeptide whose dysregulation has been associated with depression. In this review, we summarized the role of CRF in the neuroimmune mechanisms of depression, and the potential therapeutic effects of Chinese herbal medicines (CHM) as well as other agents. Studying the network of CRF and immune responses will help to enhance our understanding of the pathogenesis of depression. Additionally, targeting this important network may aid in developing novel treatments for this debilitating psychiatric disorder.

Approximately 3% of the world population suffers from depression, which is one of the most common form of mental disorder. Recent findings suggest that an interaction between the nervous system and immune system might be behind the pathophysiology of various neurological and psychiatric disorders, including depression. Neuropeptides have been shown to play a major role in mediating response to stress and inducing immune activation or suppression. Corticotropin releasing factor (CRF) is a major regulator of the hypothalamic pituitary adrenal (HPA) axis response. CRF is a stress-related neuropeptide whose dysregulation has been associated with depression. In this review, we summarized the role of CRF in the neuroimmune mechanisms of depression, and the potential therapeutic effects of Chinese herbal medicines (CHM) as well as other agents. Studying the network of CRF and immune responses will help to enhance our understanding of the pathogenesis of depression. Additionally, targeting this important network may aid in developing novel treatments for this debilitating psychiatric disorder. [ABSTRACT FROM AUTHOR]

Pain is complex. It is no longer acceptable to consider pain solely as a peripheral phenomenon involving activation of nociceptive neurons. The contemporary understanding of pain involves consideration of different underlying pain mechanisms and an increasing awareness of plasticity in all of the biological systems. Of note, recent advances in technology and understanding have highlighted the critical importance of neuroimmune interactions, both in the peripheral and central nervous systems, and the interaction between the nervous system and body tissues in the development and maintenance of pain, including low back pain (LBP). Further, the biology of many tissues changes when challenged by pain and injury, as reported in a growing body of literature on the biology of muscle, fat, and connective tissue. These advances in understanding of the complexity of LBP have implications for our understanding of pain and its interaction with the motor system, and may change how we consider motor control in the rehabilitation of LBP. This commentary provides a state-of-the-art overview of plasticity of biology in LBP. The paper is divided into 4 parts that address (1) biology of pain mechanisms, (2) neuroimmune interaction in the central nervous system, (3) neuroimmune interaction in the periphery, and (4) brain and peripheral tissue interaction. Each section considers the implications for clinical management of LBP. [ABSTRACT FROM AUTHOR]

The neuroimmune and neuroendocrine systems are two critical biological systems in the pathogenesis of depression. Clinical and preclinical studies have demonstrated that the activation of the neuroinflammatory response of the immune system and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis of the neuroendocrine system commonly coexist in patients with depression and that these two systems bidirectionally regulate one another through neural, immunological, and humoral intersystem interactions. The neuroendocrine-immune network poses difficulties associated with the development of antidepressant agents directed toward these biological systems for the effective treatment of depression. On the other hand, multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic pharmacotherapy of depression. In this narrative essay, we conclusively analyze the mechanisms of action of CHM antidepressant constituents and formulas, specifically through the modulation of the neuroendocrine-immune network, by reviewing recent preclinical studies conducted using depressive animal models. Some CHM herbal constituents and formulas are highlighted as examples, and their mechanisms of action at both the molecular and systems levels are discussed. Furthermore, we discuss the crosstalk of these two biological systems and the systems pharmacology approach for understanding the system-wide mechanism of action of CHM on the neuroendocrine-immune network in depression treatment. The holistic, multidrug, and multitarget nature of CHM represents an excellent example of systems medicine in the effective treatment of depression.

Highlights • C1 neurons are involved in the anti-inflammatory response. • Sympathoexcitation is required for anti-inflammatory response via C1 neurons. • C1 neurons are involved in the cholinergic anti-inflammatory pathway. Abstract Neuroimmune communication, the connection between the autonomic regulatory pathway and immune cells, has been implicated in the regulation of immune function and inflammation. The role of afferents (vagal afferent and somatic sensory nerves) and efferents (autonomic nervous and hypothalamic-pituitary-adrenal systems) in the inflammatory reflex has been well studied; however, the central pathway remains unknown. C1 neurons include both catecholaminergic and glutamatergic neurons, which are located in the rostral ventrolateral medulla. C1 neurons project to the spinal cord, dorsal motor nucleus of the vagus, and hypothalamus to regulate the sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems, respectively. Because C1 neurons respond to stressors, including inflammation, hypotension, hypoxia, and hypoglycemia, it is believed that the autonomic regulatory pathway, via C1 neurons, contributes to the maintenance of physiological homeostasis. Recently, selective neural manipulation has revealed that C1 neurons participate in restraint stress-induced anti-inflammation, and protection against acute kidney injury has been attributed to stress-induced sympathoexcitation through C1 neurons. We focus here on the role of C1 neurons, which act as mediators between afferents and efferents, in the anti-inflammatory pathway. [ABSTRACT FROM AUTHOR]

Aims Cardiac inflammation has been suggested to be regulated by the sympathetic nervous system (SNS) However, due to the lack of methodology to surgically eliminate the myocardial SNS in mice, neuronal control of cardiac inflammation remains ill-defined Here, we report a procedure for local cardiac sympathetic denervation in mice and tested its effect in a mouse model of heart failure post-myocardial infarction Methods and results Upon preparation of the carotid bifurcation, the right and the left superior cervical ganglia were localized and their pre- and postganglionic branches dissected before removal of the ganglion Ganglionectomy led to an almost entire loss of myocardial sympathetic innervation in the left ventricular anterior wall When applied at the time of myocardial infarction (MI), cardiac sympathetic denervation did not affect acute myocardial damage and infarct size In contrast, cardiac sympathetic denervation significantly attenuated chronic consequences of MI, including myocardial inflammation, myocyte hypertrophy, and overall cardiac dysfunction Conclusion These data suggest a critical role for local sympathetic control of cardiac inflammation Our model of myocardial sympathetic denervation in mice should prove useful to further dissect the molecular mechanisms underlying cardiac neural control [ABSTRACT FROM AUTHOR]

Trichloroethylene (TCE) is one of the most common ground water contaminants in USA. Even though recent regulation mandates restricted utilization of TCE, its use is not completely prohibited, especially in industrial and manufacturing processes. The risk of TCE on human health is an ongoing field of study and its implications on certain diseases such as cancer has been recognized and well-documented. However, the link between TCE and immune disorders is still an under-studied area. Studies on the risk of TCE on the immune system is usually focused on certain immune class disorders, but consensus on the impact of TCE on the immune system has not been established. This review presents representative work that investigates the effect of TCE on immune disorders and highlights future opportunities. We attempt to provide a broader perspective of the risks of TCE on the immune system and human health. [ABSTRACT FROM AUTHOR]

Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the 'drinking in the dark' (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption. [ABSTRACT FROM AUTHOR]

Sleep and stress have complex interactions that are implicated in both physical diseases and psychiatric disorders. These interactions can be modulated by learning and memory, and involve additional interactions with the neuroimmune system. In this paper, we propose that stressful challenges induce integrated responses across multiple systems that can vary depending on situational variables in which the initial stress was experienced, and with the ability of the individual to cope with stress- and fear-inducing challenges. Differences in coping may involve differences in resilience and vulnerability and/or whether the stressful context allows adaptive learning and responses. We provide data demonstrating both common (corticosterone, SIH and fear behaviors) and distinguishing (sleep and neuroimmune) responses that are associated with an individual's ability to respond and relative resilience and vulnerability. We discuss neurocircuitry regulating integrated stress, sleep, neuroimmune and fear responses, and show that responses can be modulated at the neural level. Finally, we discuss factors that need to be considered in models of integrated stress responses and their relevance for understanding stress-related disorders in humans., Competing Interests: None., (© 2023 The Authors.)

Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and were randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased the levels of triglyceride, hepatic stellate cell (HSC) activation factors, and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocellular carcinoma (HCC), collagen deposition, numbers of preneoplastic foci, levels of HSC activation factors and catecholamines, as well as inflammatory milieu and increased the levels of natural killer cell cytotoxic factors in the liver. Conclusions These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and HCC formation possibly via influencing the immune function. [ABSTRACT FROM AUTHOR]

The neuroimmune system (i.e., the immune system and those components of the nervous system that help regulate immune responses), and in particular the innate immune system, play a role in the development of addictions, including alcoholism, particularly in the context of stressful situations. Certain cells of the neuroimmune system are activated both by stress and by environmental factors such as alcohol, resulting in the induction of genes involved in innate immunity one of the molecules mediating this gene induction is a regulatory protein called nuclear factor-κB, which activates many innate immune genes. Innate immune gene induction in certain brain regions (e.g., the frontal cortex), in turn, can disrupt decision making, which is a characteristic of addiction to alcohol and other drugs. Likewise, altered neuroimmune signaling processes are linked to alcohol-induced negative affect and depression-like behaviors and also regulate alcohol-drinking behavior. Moreover, the expression of several genes and proteins involved in innate immunity is enhanced in addicted people. Finally, specifc variants of multiple innate immune genes are associated with the genetic risk for alcoholism in humans, further strengthening the connection between increased brain innate immune gene expression and alcohol addiction. [ABSTRACT FROM AUTHOR]

Abstract: The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) was held on June 26, 2010 in San Antonio, TX, as a satellite of the Research Society on Alcoholism meeting. The FASDSG membership includes clinical, basic, and social scientists who meet to discuss recent advances and issues in Fetal Alcohol Spectrum Disorder (FASD) research. The central theme of the meeting was “Glia and Neurons: Teamwork in Pathology and Therapy.” Alcohol disruption of neuron development and alcohol-induced neurodegeneration is central to the pathology and clinical expression of FASD. The active role of glia as perpetrator, victim, or bystander in neurotoxicology and neurodegenerative processes has emerged at the forefront of adult central nervous system (CNS) disorders and therapy. Glia– and neuron–glial interactions hold the potential to elucidate causes and offer treatment of FASD as well. Growing evidence indicates that neurons and glia are direct targets of alcohol, but may also be vulnerable to molecules produced in peripheral systems as a result of alcohol exposure. Diagnostics and therapies can take advantage of these processes and biomarkers, and these may be applicable to CNS pathology in FASD. Two keynote speakers, Howard E. Gendelman, M.D., and Ernest M. Graham, M.D, addressed the role of glia and neuroinflammation in brain development and neurodegeneration. The invited speakers and FASDSG members discussed new paradigms in CNS development and discuss new strategies for understanding and treating neurodegenerative disease. Members of the FASDSG provided updates on new findings through presentation of breaking research in the FASt data sessions. Representatives of national agencies provided updates on programs, activities, and funding priorities. The Henry Rosett Award was presented to R. Louise Floyd, R.N., D.S.N., for her career contributions to the field of fetal alcohol research. The Student and Postdoctoral Fellow Research Merit Award was presented to Shonagh O’Leary-Moore, Ph.D., for her contributions to the field as a young investigator. [Copyright &y& Elsevier]