Sistema Psiconeuroendócrino-imunitário e a Homeopatia

Trata-se de um tema que apresenta paralelos com a Homeopatia, uma vez que é voltado à totalidade do organismo. Na atualidade muitos estudos são voltados a esse novo paradigma. Aborda-se a resistência oferecida pelo modelo mecanicista/fragmentado da medicina dominante.

Ciprofloxacin and dexamethasone in combination attenuate S. aureus induced brain abscess via neuroendocrine-immune interaction of TLR-2 and glucocorticoid receptor leading to behavioral improvement.

Staphylococcus aureus induced brain abscess is a critical health concern throughout the developing world. The conventional surgical intervention could not regulate the abscess-induced brain inflammation. Thus further study over the alternative therapeutic strategy for treating a brain abscess is of high priority. The resident glial cells recognize the invading S. aureus by their cell surface Toll-like receptor-2 (TLR-2). Glucocorticoid receptor (GR) was known for its immunosuppressive effects. In this study, an attempt had been taken to utilize the functional relationship or cross-talking between TLR-2 and GR during the pathogenesis of brain abscesses. Here, the combination of an antibiotic (i.e. ciprofloxacin) and dexamethasone was used to regulate the brain inflammation either in TLR-2 or GR blocking condition. We were also interested to figure out the possible impact of alternative therapy on behavioral impairments. The results indicated that combination treatment during TLR-2 blockade significantly reduced the bacterial burden and abscess area score in the infected brain. However, marked improvements were observed in anxiety, depression-like behavior, and motor co-ordination. The combination treatment after TLR-2 blocking effectively scavenged free radicals (H2O2, superoxide anion, and NO) through modulating antioxidant enzyme activities that ultimately control S. aureus induced glial reactivity possibly via up-regulating GR expression. The exogenous dexamethasone might regulate the GR expression in the brain by increasing the corticosterone concentration and the GC-GR mediated signaling. Therefore, this in-vivo study demonstrates the possible regulatory mechanism of bacterial brain abscess that involved TLR-2 and GR as a part of neuroendocrine-immune interaction.

Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease.

The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHß made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHß splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

Adolescent social instability stress leads to immediate and lasting sex-specific changes in the neuroendocrine-immune-gut axis in rats.

Social instability stress (SS; daily 1 h isolation and change of cage partner from postnatal day (P) 30-45) in adolescence produces elevations in corticosterone during the procedure in male and female rats, but no lasting changes in hypothalamic-pituitary-adrenal (HPA) responses to psychological stressors, although deficits in social and cognitive function are evident in adulthood. Here we investigated the effects of SS in corticosterone response to an immune challenge (lipopolysaccharide, LPS, 0.1 mg/kg), on gene expression in the hippocampus, and on gut microbiota, when tested soon- (P46) or long- (P70) after SS. The temporal pattern of corticosterone release after LPS differed between SS and control rats irrespective of the time since SS exposure in females, whereas in males, SS did not alter corticosterone release after LPS. Expression of genes in the hippocampus relevant to immune and HPA function differed between saline-treated SS and control rats depending on sex and time tested, but with lasting consequences of SS in both sexes. LPS-treatment altered hippocampal gene expression, with bigger effects of LPS evident in control than in SS female rats, and the opposite in male rats. Further, effects sometimes depended on the age at time of LPS treatment. SS and control rats differed in both fecal and colon microbiome composition in all but P46 males, and stress history, sex, and age influenced the effects of an immune challenge on the gut microbiome. In sum, adolescent stress history has consequences for immune function into adulthood that may involve effects on the gut microbiome.

Role of novel protein kinase C in neuroendocrine-immune regulatory network in haemocytes of Litopenaeus vannamei: An in vitro approach.

Shrimp lack adaptive immune systems and mainly rely on the cellular and humoral defences, involving the haemocytes (functionally analogous to vertebrate leukocytes) in non-self matter recognition, elimination, and in downstream coagulation. Furthermore, the linkage between stress-induced catecholamine (CA), a class of biogenic amines (BAs), releasing and immunological responses has been detected in shrimp. Varied isotypes of protein kinase C (PKC) regulate multiple cellular processes following their specific location and distribution within the cells, and a novel PKC identified in Litopenaeus vannamei (termed as LvnPKC) is proposed to mediate signaling transduction of immunocompetence and BA biosynthesis. In the present study, we analyzed the effects of the LvnPKC-silenced haemocytes by co-incubating with its dsRNA on the immune responses specific to prophenoloxidase (proPO) and antioxidant systems as well as phagocytic activity. In addition, the capability of haemocytes to produce BAs was assessed. The results revealed that LvnPKC-silenced haemocytes can induce interference in phenoloxidase and superoxide dismutase activities, respiratory bursts, and phagocytic activity; meanwhile, the disturbed gene expressions of proPO activating enzyme, proPOII, lipopolysaccharide- and ß-1,3-glucan-binding protein, and cytosolic manganese superoxide dismutase were detected. The same deviated pattern was observed in tyrosine, dopamine, and norepinephrine levels, and in dopamine ß-hydroxylase (DBH) activity and gene expressions of tyrosine hydroxylase, DOPA decarboxylase, and DBH involving in BA biosynthesis. Taken together, these results suggest that the immunocompetence and BA biosynthesis of haemocytes can be mediated via LvPKC signaling transduction, which proved the presence of a neuroendocrine-immune regulatory network in haemocytes.

Hyponatremia: A possible immuno-neuroendocrine interface with COVID-19 in a kidney transplant recipient.

There is fast-emerging, cumulative clinical data on coronavirus disease 2019 (COVID-19) in kidney transplant recipients. Although respiratory tract symptoms are often the initial presentation among kidney transplant recipients who contract COVID-19, other clinical features which may indicate underlying SARS-CoV-2-related inflammation, such as gastrointestinal symptoms, are not uncommon. Hyponatremia can develop and may reflect underlying inflammation. Interferon-6 is an important pro-inflammatory cytokine involved in the pathogenesis of severe COVID-19 complications and may play a role in the inappropriately higher secretion of antidiuretic hormone leading to hyponatremia. This pathway is the so-called immuno-neuroendocrine interface. Hyponatremia in COVID-19 has been reported in a few case series of non-kidney transplant patients and only one reported kidney transplant recipient. However, the clinical course and prognostic value of hyponatremia in this population are not described in detail. We report a kidney transplant recipient who was infected with COVID-19 and exhibited severe hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. Hyponatremia is one of the clinical presentations of COVID-19, although less common, and may occur more frequently in kidney transplant recipients. Thus, the possible underlying immuno-neuroendocrine relationship related to the inflammatory process of COVID-19 leading to hyponatremia and its prognostic value are reviewed.

Perinatal Inflammation Reprograms Neuroendocrine, Immune, and Reproductive Functions: Profile of Cytokine Biomarkers.

Viral and bacterial infections causing systemic inflammation are significant risk factors for developing body. Inflammatory processes can alter physiological levels of regulatory factors and interfere with developmental mechanisms. The brain is the main target for the negative impact of inflammatory products during critical ontogenetic periods. Subsequently, the risks of various neuropsychiatric diseases such as Alzheimer's and Parkinson's diseases, schizophrenia, and depression are increased in the offspring. Inflammation-induced physiological disturbances can cause immune and behavioral disorders, reproductive deficiencies, and infertility. The influence of maternal immune stress is mediated by the regulation of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, monocyte chemotactic protein 1, leukemia-inhibiting factor, and tumor necrosis factor-alpha secretion in the maternal-fetal system. The increasing number of patients with neuronal and reproductive disorders substantiates the identification of biomarkers for these disorders targeted at their therapy.

Acute BPA exposure-induced oxidative stress, depressed immune genes expression and damage of hepatopancreas in red swamp crayfish Procambarus clarkii.

Bisphenol A is a typical endocrine disrupting chemicals (EDCs) and produce various toxic effects on animals due to its potential endocrine disruption, oxidative damage effect, mutagenic effect and hypomethylation. To study its effect on the immune system of crustaceans, the Procambarus clarkii were utilized to detect the immune related indicators after 225 µg/L BPA exposure for 1 week. Hepatopancreatic histology and ultrastructure analysis showed that the brush border disappeared, the lumen increased, and the connection between the hepatic tubules fade away in BPA treated group. BPA could significantly increase the level of ROS, inhibit the activities of antioxidant-related enzymes (SOD, POD, and CAT), and thereby cause the oxidative stress. The enzyme activities of AKP, ACP and lysozyme in hepatopancreas after BPA exposure were also depressed even after Aeromonas hydrophila infections. The relative expression profiles of immune-related genes after BPA exposure and bacterial infection showed suppressed trends of most selected genes. Under A. hydrophila infections, the cumulative mortality of 225 µg/L BPA-treated crayfish was significantly higher than other groups. All these results indicated that BPA exposure had adverse effects on the immune ability of P. clarkii. The present study will provide an important foundation for further understanding the effects of EDCs on crustacean immune functions.

Host-microbiome intestinal interactions during early life: considerations for atopy and asthma development.

PURPOSE OF REVIEW: The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobes Bifidobacteria and Bacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma. RECENT FINDINGS: Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases. SUMMARY: Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host-microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility.

Brain Angiotensinergic Regulation of the Immune System: Implications for Cardiovascular and Neuroendocrine Responses.

OBJECTIVE: The Renin-Angiotensin-Aldosterone System (RAAS) plays a major role in the regulation of cardiovascular functions, water and electrolytic balance, and hormonal responses. We perform a review of the literature, aiming at providing the current concepts regarding the angiotensin interaction with the immune system in the brain and the related implications for cardiovascular and neuroendocrine responses. METHODS: Appropriate keywords and MeSH terms were identified and searched in Pubmed. Finally, references of original articles and reviews were examined. RESULTS: Angiotensin II (ANG II), beside stimulating aldosterone, vasopressin and CRH-ACTH release, sodium and water retention, thirst, and sympathetic nerve activity, exerts its effects on the immune system via the Angiotensin Type 1 Receptor (AT 1R) that is located in the brain, pituitary, adrenal gland, and kidney. Several actions are triggered by the binding of circulating ANG II to AT 1R into the circumventricular organs that lack the Blood-Brain-Barrier (BBB). Furthermore, the BBB becomes permeable during chronic hypertension thereby ANG II may also access brain nuclei controlling cardiovascular functions. Subfornical organ, organum vasculosum lamina terminalis, area postrema, paraventricular nucleus, septal nuclei, amygdala, nucleus of the solitary tract and retroventral lateral medulla oblongata are the brain structures that mediate the actions of ANG II since they are provided with a high concentration of AT 1R. ANG II induces also T-lymphocyte activation and vascular infiltration of leukocytes and, moreover, oxidative stress stimulating inflammatory responses via inhibition of endothelial progenitor cells and stimulation of inflammatory and microglial cells facilitating the development of hypertension. CONCLUSION: Besides the well-known mechanisms by which RAAS activation can lead to the development of hypertension, the interactions between ANG II and the immune system at the brain level can play a significant role.

An overview of the neuroendocrine system in Parkinson's disease: what is the impact on diagnosis and treatment?

Introduction: A growing body of evidence indicates that neuroendocrine interactions may occur at all levels of the brain-gut-microbiota axis, which is directly involved in the pathogenesis of Parkinson's disease (PD).Areas covered: The review presents some current and emerging concepts regarding the organization and functioning of the neuroendocrine system as well as the role of neuroendocrine disturbances in the pathophysiology and symptomatology of PD. The concept of the brain-gut-microbiota triad interactions in the neuroendocrine system and PD is proposed. In PD, dysregulation of the main neuroendocrine axes coordinated by the hypothalamus is accompanied by disruptions at the peripheral level, which involve enteroendocrine cells producing numerous neuropeptides. Moreover, the important role of the gut microbiota as a main coordinator of immune and neuroendocrine interactions is discussed. The potential diagnostic and therapeutic implications in the context of the recent developments in the fields of neuroendocrinology and neurodegeneration are also presented.Expert opinion: Unraveling complex neuroendocrine interactions in the course of PD may provide crucial diagnostic implications and novel therapeutic approaches including the application of gut neuropeptides and gut microbiota modification.

Is the Cerebellum Involved in the Nervous Control of the Immune System Function?

BACKGROUND: According to the views of psychoneuroendocrinoimmunology, many interactions exist between nervous, endocrine and immune system the purpose of which is to achieve adaptive measures restoring an internal equilibrium (homeostasis) following stress conditions. The center where these interactions converge is the hypothalamus. This is a center of the autonomic nervous system that controls the visceral systems, including the immune system, through both the nervous and neuroendocrine mechanisms. The nervous mechanisms are based on nervous circuits that bidirectionally connect hypothalamic neurons and neurons of the sympathetic and parasympathetic system; the neuroendocrine mechanisms are based on the release by neurosecretory hypothalamic neurons of hormones that target the endocrine cells and on the feedback effects of the hormones secreted by these endocrine cells on the same hypothalamic neurons. Moreover, the hypothalamus is an important subcortical center of the limbic system that controls through nervous and neuroendocrine mechanisms the areas of the cerebral cortex where the psychic functions controlling mood, emotions, anxiety and instinctive behaviors take place. Accordingly, various studies conducted in the last decades have indicated that hypothalamic diseases may be associated with immune and/or psychic disorders. OBJECTIVE: Various researches have reported that the hypothalamus is controlled by the cerebellum through a feedback nervous circuit, namely the hypothalamocerebellar circuit, which bi-directionally connects regions of the hypothalamus, including the immunoregulatory ones, and related regions of the cerebellum. An objective of the present review was to analyze the anatomical bases of the nervous and neuroendocrine mechanisms for the control of the immune system and, in particular, of the interaction between hypothalamus and cerebellum to achieve the immunoregulatory function. CONCLUSION: Since the hypothalamus represents the link through which the immune functions may influence the psychic functions and vice versa, the cerebellum, controlling several regions of the hypothalamus, could be considered as a primary player in the regulation of the multiple functional interactions postulated by psychoneuroendocrinoimmunology.

Neuroendocrine immune-regulatory of a neuropeptide ChGnRH from the Hongkong oyster, Crassostrea Hongkongensis.

It is increasingly appreciated that neuroendocrine-immune interactions hold the key to understand the complex immune system. In this study, we explored the role of a reproductive regulation-related hormone, GnRH, in the regulation of immunity in Hong Kong oysters. We found that vibrio bacterial strains injection increased the expression of ChGnRH. Moreover, ChGnRH neuropeptide promotes the phagocytic ability and bacterial clearance effect of hemocytes which regarded to be the central immune organ. The content of cAMP after incubation with ChGnRH peptide was increased, which could be blocked by adenylyl cyclase inhibitor SQ 22,536. Furthermore, the stimulated effect of ChGnRH peptide on the phagocytosis and bacterial clearance was also blocked by SQ 22,536, H89 and enzastaurin, strongly demonstrating that cAMP dependent PKA and PKC signaling pathway was involved in ChGnRH mediated immune regulation. In conclusion, this study confirms the presence of neuroendocrine-immune regulatory system in marine invertebrates, which contributes to understand the complexity of oyster immune defense system.

Transcriptome analysis reveals the activation of neuroendocrine-immune system in shrimp hemocytes at the early stage of WSSV infection.

BACKGROUND: Functional communications between nervous, endocrine and immune systems are well established in both vertebrates and invertebrates. Circulating hemocytes act as fundamental players in this crosstalk, whose functions are conserved during the evolution of the main groups of metazoans. However, the roles of the neuroendocrine-immune (NEI) system in shrimp hemocytes during pathogen infection remain largely unknown. RESULTS: In this study, we sequenced six cDNA libraries prepared with hemocytes from Litopenaeus vannamei which were injected by WSSV (white spot syndrome virus) or PBS for 6 h using Illumina Hiseq 4000 platform. As a result, 3444 differentially expressed genes (DEGs), including 3240 up-regulated genes and 204 down-regulated genes, were identified from hemocytes after WSSV infection. Among these genes, 349 DEGs were correlated with innate immunity and categorized into seven groups based on their predictive function. Interestingly, 18 genes encoded putative neuropeptide precursors were induced significantly by WSSV infection. Furthermore, some genes were mapped to several typical processes in the NEI system, including proteolytic processing of prohormones, amino acid neurotransmitter pathways, biogenic amine biosynthesis and acetylcholine signaling pathway. CONCLUSIONS: The data suggested that WSSV infection triggers the activation of NEI in shrimp, which throws a light on the pivotal roles of NEI system mediated by hemocytes in shrimp antiviral immunity.

Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling.

The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria. Neuroendocrine pathway genes are upregulated by intestinal bloating and are required for microbial aversion behavior. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. These results reveal how inputs from the intestine can aid in the recognition of a broad range of microbes and modulate host behavior via neuroendocrine signaling.

Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases.

Health, pre-disease and critical transition to disease in the psycho-immune-neuroendocrine network: Are there distinct states in the progression from health to major depressive disorder?

The psycho-immune-neuroendocrine (PINE) network is a regulatory network of interrelated physiological pathways that have been implicated in major depressive disorder (MDD). A model of disease progression for MDD is presented where the stable, healthy state of the PINE network (PINE physiome) undergoes progressive pathophysiological changes to an unstable but reversible pre-disease state (PINE pre-diseasome) with chronic stress. The PINE network may then undergo critical transition to a stable, possibly irreversible disease state of MDD (PINE pathome). Critical transition to disease is heralded by early warning signs which are detectible by biomarkers specific to the PINE network and may be used as a screening test for MDD. Critical transition to MDD may be different for each individual, as it is reliant on diathesis, which comprises genetic predisposition, intrauterine and developmental factors. Finally, we propose the PINE pre-disease state may form a "universal pre-disease state" for several non-communicable diseases (NCDs), and critical transition of the PINE network may lead to one of several frequently associated disease states (influenced by diathesis), supporting the existence of a common Chronic Illness Risk Network (CIRN). This may provide insight into both the puzzle of multifinality and the growing clinical challenge of multimorbidity.

The immune system as a sensorial system that can modulate brain functions and reset homeostasis.

Evidence indicates that activated immune cells release products, typically cytokines, that can convey information to the brain about the type of ongoing peripheral immune responses. This evidence led colleagues and me to categorize the immune system as another sensorial system that, upon receiving this information, can emit neuroendocrine signals with immunoregulatory functions that can also reset homeostatic mechanisms. Here, I discuss evidence and clues indicating (1) possible mechanisms by which cytokines, such as those of the interleukin 1 (IL-1) family, can reset energy homeostasis to balance the high fuel requirement of the immune system and the brain; and (2) the possibility that the tripartite synapse, which includes astrocytes as a third component, processes and integrates immune signals at brain levels with other sensorial signals that the central nervous system permanently receives.

The Heart as a Psychoneuroendocrine and Immunoregulatory Organ.

The heart can be viewed not just as muscle pump but also as an important checkpoint for a complex network of nervous, endocrine, and immune signals. The heart is able to process neurological signals independently from the brain and to crosstalk with the endocrine and immune systems. The heart communicates with the psyche through the neuro-endocrine-immune system in a highly integrated way, in order to maintain the homeostasis of the whole body with peculiarities specific to males and females.