Relationships between short and fast brain timescales

Brain electric activity exhibits two important features: oscillations with different timescales, characterized by diverse functional and psychological outcomes, and a temporal power law distribution. In order to further investigate the relationships between low- and high- frequency spikes in the brain, we used a variant of the Borsuk–Ulam theorem which states that, when we assess the nervous activity as embedded in a sphere equipped with a fractal dimension, we achieve two antipodal points with similar features (the slow and fast, scale-free oscillations). We demonstrate that slow and fast nervous oscillations mirror each other over time via a sinusoid relationship and provide, through the Bloch theorem from solid-state physics, the possible equation which links the two timescale activities. We show that, based on topological findings, nervous activities occurring in micro-levels are projected to single activities at meso- and macro-levels. This means that brain functions assessed at the higher scale of the whole brain necessarily display a counterpart in the lower ones, and vice versa. Our topological approach makes it possible to assess brain functions both based on entropy, and in the general terms of particle trajectories taking place on donut-like manifolds. Condensed brain activities might give rise to ideas and concepts by combination of different functional and anatomical levels. Furthermore, cognitive phenomena, as well as social activity can be described by the laws of quantum mechanics; memories and decisions exhibit holographic organization. In physics, the term duality refers to a case where two seemingly different systems turn out to be equivalent. This topological duality holds for all the types of spatio-temporal brain activities, independent of their inter- and intra-level relationships, strength, magnitude and boundaries, allowing us to connect the physiological manifestations of consciousness to the electric activities of the brain.     

Relationships between gene expression and brain wiring in the adult rodent brain

We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain "connectome" from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS.     

Stress and immunity: an integrated view of relationships between the brain and the immune system

The old notion that stress exacerbates the progression of physical illness via its corticosteroid-mediated immunosuppressive effects must be revised. Experimental and clinical studies demonstrate that both laboratory and natural stressors alter the activities of lymphocytes and macrophages in a complex way that depends on the type of immune response, the physical and psychological characteristics of the stressor and the timing of stress relative to the induction and expression of the immune event. The influences of stress on immunity are mediated not only by glucocorticoids but also by catecholamines, endogenous opioids and pituitary hormones such as growth hormone. Sensitivity of the immune system to stress is not simply fortuitous but is an indirect consequence of the regulatory reciprocal influences that exist between the immune system and the central nervous system. The immune system receives signals from the brain and the neuroendocrine system via the autonomic nervous system and hormones and sends information to the brain via cytokines. These connections appear to be part of a long-loop regulatory feedback system that plays an important role in the coordination of behavioral and physiological responses to infection and inflammation.     

The dynamic interplay between osteoclasts and the immune system

Investigation into arthritis, as well as numerous bone phenotypes found in mice lacking immune-related genes, has highlighted the importance of the interplay between the bone and immune systems, which has led to the emergence and evolution of the field of osteoimmunology. RANKL stimulates osteoclastogenesis through nuclear factor of activated T cells (NFAT) c1, which is also a crucial regulator of immunity. In rheumatoid arthritis, bone destruction is caused by the enhanced activity of osteoclasts, which is mainly dependent on interleukin-17-producing helper T cells (T_H17). The scope of osteoimmunology has been extended to encompass a wide range of molecular and cellular interactions. The framework of osteoimmunology will provide a scientific basis for future therapeutic approaches to diseases related to both of these systems.     

Interactions between mycoplasma lipoproteins and the host immune system

Mycoplasmas typically have a number of distinct lipoproteins anchored on the outer face of the plasma membrane. These surface antigens have a potent modulin activity and are preferential targets of the host immune response. However, the variation of some of these lipoproteins provides mycoplasmas with an effective means of evading the host immune defence system.     

神经内分泌和免疫系统之间的相互调节作用(一)

我们一般认为机体各器官、系统的功能都处于神经系统和内分泌系统的调节和控制之下。神经系统和内分泌系统是机体内起主导作用的调节系统。它们密切联系 ,互相配合 ,维持内环境相对稳定。这一传统的观念近年来受到了挑战。新的观点认为 ,免疫系统也是机体内一个重要感受和调节系统。神经内分泌和免疫系统之间的相互作用 ,对机体在不同条件下稳态的维持起有决定性的作用。因此 ,在谈到机体的功能调节时 ,如果不谈免疫系统的作用 ,将是一种缺陷。目前这方面的研究已经发展成为一门独立的边缘学科 :神经免疫调节学、神经免疫内分泌学或神经免疫…     

Bidirectional communication between the pineal gland and the immune system

The pineal gland is a vertebrate neuroendocrine organ converting environmental photoperiodic information into a biochemical message (melatonin) that subsequently regulates the activity of numerous target tissues after its release into the bloodstream. A phylogenetically conserved feature is increased melatonin synthesis during darkness, even though there are differences between mammals and birds in the regulation of rhythmic pinealocyte function. Membrane-bound melatonin receptors are found in many peripheral organs, including lymphoid glands and immune cells, from which melatonin receptor genes have been characterized and cloned. The expression of melatonin receptor genes within the immune system shows species and organ specificity. The pineal gland, via the rhythmical synthesis and release of melatonin, influences the development and function of the immune system, although the postreceptor signal transduction system is poorly understood. Circulating messages produced by activated immune cells are reciprocally perceived by the pineal gland and provide feedback for the regulation of pineal function. The pineal gland and the immune system are, therefore, reciprocally linked by bidirectional communication.     

Crosstalk between the circadian clock circuitry and the immune system

Various features, components, and functions of the immune system present daily variations. Immunocompetent cell counts and cytokine levels present variations according to the time of day and the sleep-wake cycle. Moreover, different immune cell types, such as macrophages, natural killer cells, and lymphocytes, contain a circadian molecular clockwork. The biological clocks intrinsic to immune cells and lymphoid organs, together with inputs from the central pacemaker of the suprachiasmatic nuclei via humoral and neural pathways, regulate the function of cells of the immune system, including their response to signals and their effector functions. Consequences of this include, for example, the daily variation in the response to an immune challenge (e.g., bacterial endotoxin injection) and the circadian control of allergic reactions. The circadian-immune connection is bidirectional, because in addition to this circadian control of immune functions, immune challenges and immune mediators (e.g., cytokines) were shown to have strong effects on circadian rhythms at the molecular, cellular, and behavioral levels. This tight crosstalk between the circadian and immune systems has wide-ranging implications for disease, as shown by the higher incidence of cancer and the exacerbation of autoimmune symptoms upon circadian disruption. (Author correspondence: g.mazzoccoli@operapadrepio.it)     

Relationships between ethylenediamine and GABA transport systems in rat brain slices

[¹⁴C]EDA was accumulated by slices of adult rat cerebral cortex, although the tissue:medium ratios achieved were very much lower than those for GABA. EDA uptake was temperature dependent and appeared to take place by both sodium dependent and sodium independent mechanisms. Kinetic analysis of the uptake revealed a major low affinity component with an apparent K_m of 1.11 ± 0.05 mM and a V_max of 9.8 ± 0.2 μmol/hg wet wt, with a second site of K_m about 20 μM but a 50 fold lower V_max. Inhibition studies indicate that EDA may be transported in part by the ‘small basic’ amino acid transport system and in part by polyamine systems shown to be present in CNS tissue. High levels of displaceable binding of radioactive EDA to glass-fibre filters were observed; studies using [¹⁴C]EDA may be complicated by binding to tissue macromolecules. Potassium stimulated, calcium dependent release of radioactivity from brain slices labelled with [¹⁴C]EDA in the presence of sodium ions was observed. Extracellular EDA stimulated the release of [³H]GABA and [³H]beta-alanine from preloaded slices, although GABA and beta-alanine did not stimulate [¹⁴C]EDA release. It appears that extracellular EDA can counterexchange with intracellular GABA or beta-alanine, but that EDA which is accumulated by the tissue may then be bound or move to pools not directly accessible to these amino acids. Ouabain released radioactivity from slices labelled by [¹⁴C]EDA in the presence of sodium but not from slices labelled in the absence of sodium. These results suggests that EDA is not acting simply as a substrate for GABA transport sites.     

Interplay between Kaposi's sarcoma-associated herpesvirus and the innate immune system

Understanding of the innate immune response to viral infections is rapidly progressing, especially with regards to the detection of DNA viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) is a large dsDNA virus that is responsible for three human diseases: Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. The major target cells of KSHV (B cells and endothelial cells) express a wide range of pattern recognition receptors (PRRs) and play a central role in mobilizing inflammatory responses. On the other hand, KSHV encodes an array of immune evasion genes, including several pirated host genes, which interfere with multiple aspects of the immune response. This review summarizes current understanding of innate immune recognition of KSHV and the role of immune evasion genes that shape the antiviral and inflammatory responses.     

神经内分泌和免疫系统之间的相互作用(二)——神经免疫调节

(上接 2 0 0 0年第 3期第 3页 )1 .6.2　某些前激素 (prohormone)的作用　血液循环中的硫酸表甾酮 (dehydroepiandrosteronesulphate,DHEAS)受到 DHEA硫酸酶的作用变成 DHEA可增强 TH1的活性 ,此时 TH1/TH2 的比值趋向于 TH1占优势。随着年龄的增加 DHEA的水平也随之下降。这可能是机体随着年龄的增长免疫功能下降的重要原因之一。动物实验中也发现 ,老年鼠体内的 DHEA含量明显低于对照组。如果补充 DHEA后老年鼠的免疫缺损状态可以得到明显改善。此外 ,衰老时的免疫功能下降也与某些细胞因子分泌异常增高有关。例如 IL -6的…     

The link between small heat shock proteins and the immune system

There is now compelling evidence that members of the family of small heat shock proteins (HSP) can be secreted by a variety of different types of cells. Secretion of small HSP may at times represent altruistic delivery of supporting and stabilizing factors from one cell to another. A probably more general effect of extracellular small HSP, however, is exerted by their ability to activate macrophages and macrophage-like cells. When doing so, small HSP induce an immune-regulatory state of activation, stimulating macrophages to suppress inflammation. For this reason, small HSP deserve consideration as broadly applicable therapeutic agents for inflammatory disorders. In one particular case, however, adaptive immune responses to the small HSP itself may subvert the protective quality of the innate immune response it triggers. This situation only applies to alpha B-crystallin, and is unique for humans as well. In this special case, local concentrations of alpha B-crystallin determine the balance between protective innate responses and destructive adaptive responses, the latter of which are held responsible for the development of multiple sclerosis lesions. This article is part of a Directed Issue entitled: Small HSPs in physiology and pathology.     

Molecular cross talk between Toxoplasma gondii and the host immune system

Toxoplasma gondii is an intracellular parasite that frequently infects a large spectrum of warm-blooded animals. This parasite induces abortion and establishes both chronic and silent infections, particularly in the brain. The chronic infection is therefore a permanent threat for the host in cases of immunosuppression. Parasite penetration into the host activates a strong anti-parasite immune response, but is also used by the parasite to chronically persist. In the present paper, we discuss the data obtained in the laboratory of John Boothroyd that reports the molecular cross talk between the parasite rhoptry proteins and the host cell. During host cell invasion, rhoptries participate to the constitution of the mobile junction that drives the parasite into the host cell, while building the parasitophorus vacuole in which the parasite grows. Some soluble rhoptries, such as ROP16, are shed into the cytoplasm, and then reach the nucleus where they can eventually impact different signaling pathways such as STAT3/6, key molecules in the immune response establishment.     

From inflammation to sickness and depression: when the immune system subjugates the brain

In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.