Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system ("neuroinflammation"), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell-cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenous mechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation.

/pdf/an-inflammation-centric-view-of-neurological-disease-beyond-fqti23l27r.pdf

An Inflammation-Centric View of Neurological Disease: Beyond the Neuron.

Cancer starts as a localised disease, which, if detected early, can often be treated successfully by removal of the primary tumour. A pernicious progression is the invasion of tumour cells into surrounding tissues, resulting in development of distant metastases. Because active migration of tumour cells is a prerequisite for tumour-cell invasion and metastasis, a pressing goal in tumour biology has been the elucidation of factors regulating the migratory activity of these cells. The most prominent regulatory factors are ligands to serpentine receptors-eg, chemokines and neurotransmitters. Many types of neurotransmitter receptors are expressed on tumour cells, supporting the theory that psychosocial factors are involved in the progression of cancer. Understanding how such receptors regulate migration and the availability of specific receptor antagonists could open up new avenues for chemoprevention of tumour-cell migration and metastatic development.

Iconography : Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters

The contribution of nerves to the pathogenesis of malignancies has emerged as an important component of the tumour microenvironment. Recent studies have shown that peripheral nerves (sympathetic, parasympathetic and sensory) interact with tumour and stromal cells to promote the initiation and progression of a variety of solid and haematological malignancies. Furthermore, new evidence suggests that cancers may reactivate nerve-dependent developmental and regenerative processes to promote their growth and survival. Here we review emerging concepts and discuss the therapeutic implications of manipulating nerves and neural signalling for the prevention and treatment of cancer. This Review discusses the role that nerves play in the initiation and progression of cancers, focusing on the evidence that tumours may reactivate nerve-mediated developmental and regenerative pathways to promote their own growth and survival.

Nerves in cancer

Long Road to Ruin: Noradrenergic Dysfunction in Neurodegenerative Disease.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new pandemic infectious disease that originated in China. COVID-19 is a global public health emergency of international concern. COVID-19 causes mild to severe illness with high morbidity and mortality, especially in preexisting risk groups. Therapeutic options are now limited to COVID-19. The hallmark of COVID-19 pathogenesis is the cytokine storm with elevated levels of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-alpha (TNF-α), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF). COVID-19 can cause severe pneumonia, and neurological disorders, including stroke, the damage to the neurovascular unit, blood-brain barrier disruption, high intracranial proinflammatory cytokines, and endothelial cell damage in the brain. Mast cells are innate immune cells and also implicated in adaptive immune response, systemic inflammatory diseases, neuroinflammatory diseases, traumatic brain injury and stroke, and stress disorders. SARS-CoV-2 can activate monocytes/macrophages, dendritic cells, T cells, mast cells, neutrophils, and induce cytokine storm in the lung. COVID-19 can activate mast cells, neurons, glial cells, and endothelial cells. SARS-CoV-2 infection can cause psychological stress and neuroinflammation. In conclusion, COVID-19 can induce mast cell activation, psychological stress, cytokine storm, and neuroinflammation.

https://journals.sagepub.com/doi/pdf/10.1177/1073858420941476

COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation.

The development and progression of cancer depends on both tumor micro- and macroenvironments. In addition, psychosocial and spiritual "environments" might also affect cancer. It has been found that the nervous system, via neural and humoral pathways, significantly modulates processes related to cancer at the level of the tumor micro- and macroenvironments. The nervous system also mediates the effects of psychosocial and noetic factors on cancer. Importantly, data accumulated in the last two decades have clearly shown that effects of the nervous system on cancer initiation, progression, and the development of metastases are mediated by the sympathoadrenal system mainly via β-adrenergic receptor signaling. Here, we provide a new complex view of the role of β-adrenergic receptor signaling within the tumor micro- and macroenvironments as well as in mediating the effects of the psychosocial and spiritual environments. In addition, we describe potential preventive and therapeutic implications.

https://www.mdpi.com/1422-0067/21/21/7958/pdf

Neurobiology of Cancer: the Role of β-Adrenergic Receptor Signaling in Various Tumor Environments

Stress and cancer. Part I: Mechanisms mediating the effect of stressors on cancer.

From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.

/pdf/e-cigarettes-and-cancer-risk-b34k713tze.pdf

E-Cigarettes and Cancer Risk

Modern society is characterized by the ubiquity of stressors that affect every individual to different extents. Furthermore, experimental, clinical, and epidemiological data have shown that chronic activation of the stress response may participate in the development of various somatic as well as neuropsychiatric diseases. Surprisingly, the role that stress plays in the etiopathogenesis of Alzheimer's disease (AD) has not yet been studied in detail and is therefore not well understood. However, accumulated data have shown that neuroendocrine and behavioral changes accompanying the stress response affect neuronal homeostasis and compromise several key neuronal processes. Mediators of the neuroendocrine stress response, if elevated repeatedly or chronically, exert direct detrimental effects on the brain by impairing neuronal metabolism, plasticity, and survival. Stress-induced hormonal and behavioral reactions may also participate in the development of hypertension, atherosclerosis, insulin resistance, and other peripheral disturbances that may indirectly induce neuropathological processes participating in the development and progression of AD. Importantly, stress-induced detrimental effects as etiological factors of AD are attractive because they can be reduced by several approaches including behavioral and pharmacological interventions. These interventions may therefore represent an important strategy for prevention or attenuation of the progression of AD.

Brain Under Stress and Alzheimer's Disease.

Accumulated evidence indicates that sympathetic nerves may potentiate tumor growth, including melanoma. To elucidate possible mechanisms for this effect, we performed chemical sympathectomy by intraperitoneal (i.p.) injection of the neurotoxin 6-hydroxydopamine hydrobromide (100 mg/kg of body weight); in nine adult male C57BL/6J mice; nine control mice received i.p. vehicle (VEH). Seven days later, all mice were injected subcutaneously with 3 × 103 B16-F10 melanoma cells. Mice were euthanized 20 d after injection of melanoma cells, for measurement of tumor weight and expression of genes related to sympathetic signaling, apoptosis, hypoxia and angiogenesis in tumor tissue. To assess potential involvement of the hypothalamo–pituitary–adrenocortical axis in the effect of sympathectomy on melanoma growth, concentrations of plasma corticosterone and level of glucocorticoid receptor mRNA in tumor tissue were determined. We found that sympathectomy significantly attenuated melanoma growth (tumor weight 0...

Lubica Horvathova

Papers

Neurobiology of Cancer: the Role of β-Adrenergic Receptor Signaling in Various Tumor Environments

Stress and cancer. Part I: Mechanisms mediating the effect of stressors on cancer.

E-Cigarettes and Cancer Risk

Brain Under Stress and Alzheimer's Disease.

Sympathectomy reduces tumor weight and affects expression of tumor-related genes in melanoma tissue in the mouse.