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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

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.

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.)

Inflammatory bowel disease (IBD) is a global disease that is in increasing incidence. The gut, which contains the largest amount of lymphoid tissue in the human body, as well as a wide range of nervous system components, is integral in ensuring intestinal homeostasis and function. By interacting with gut microbiota, immune cells, and the enteric nervous system, the intestinal barrier, which is a solid barrier, protects the intestinal tract from the external environment, thereby maintaining homeostasis throughout the body. Destruction of the intestinal barrier is referred to as developing a "leaky gut," which causes a series of changes relating to the occurrence of IBD. Changes in the interactions between the intestinal barrier and gut microbiota are particularly crucial in the development of IBD. Exploring the leaky gut and its interaction with the gut microbiota, immune cells, and the neuroimmune system may help further explain the pathogenesis of IBD and provide potential therapeutic methods for future use.