scholarly journals Targeting the CCL2-CCR2 axis in depressive disorders

2021 ◽  
Author(s):  
Katarzyna Curzytek ◽  
Monika Leśkiewicz
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Affective Disorders ◽  
Depressive Disorders ◽  
Brain Diseases ◽  
Receptor System ◽  
Proinflammatory Mediators ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Abnormal Brain

AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.

scholarly journals Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Davide Marangon ◽  
Nicolò Caporale ◽  
Marta Boccazzi ◽  
Maria P. Abbracchio ◽  
Giuseppe Testa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Brain Physiology ◽  
Pathological Conditions ◽  
Approaches To Study ◽  
The Central Nervous System ◽  
Experimental Approaches

Myelin is the lipidic insulating structure enwrapping axons and allowing fast saltatory nerve conduction. In the central nervous system, myelin sheath is the result of the complex packaging of multilamellar extensions of oligodendrocyte (OL) membranes. Before reaching myelinating capabilities, OLs undergo a very precise program of differentiation and maturation that starts from OL precursor cells (OPCs). In the last 20 years, the biology of OPCs and their behavior under pathological conditions have been studied through several experimental models. When co-cultured with neurons, OPCs undergo terminal maturation and produce myelin tracts around axons, allowing to investigate myelination in response to exogenous stimuli in a very simple in vitro system. On the other hand, in vivo models more closely reproducing some of the features of human pathophysiology enabled to assess the consequences of demyelination and the molecular mechanisms of remyelination, and they are often used to validate the effect of pharmacological agents. However, they are very complex, and not suitable for large scale drug discovery screening. Recent advances in cell reprogramming, biophysics and bioengineering have allowed impressive improvements in the methodological approaches to study brain physiology and myelination. Rat and mouse OPCs can be replaced by human OPCs obtained by induced pluripotent stem cells (iPSCs) derived from healthy or diseased individuals, thus offering unprecedented possibilities for personalized disease modeling and treatment. OPCs and neural cells can be also artificially assembled, using 3D-printed culture chambers and biomaterial scaffolds, which allow modeling cell-to-cell interactions in a highly controlled manner. Interestingly, scaffold stiffness can be adopted to reproduce the mechanosensory properties assumed by tissues in physiological or pathological conditions. Moreover, the recent development of iPSC-derived 3D brain cultures, called organoids, has made it possible to study key aspects of embryonic brain development, such as neuronal differentiation, maturation and network formation in temporal dynamics that are inaccessible to traditional in vitro cultures. Despite the huge potential of organoids, their application to myelination studies is still in its infancy. In this review, we shall summarize the novel most relevant experimental approaches and their implications for the identification of remyelinating agents for human diseases such as multiple sclerosis.

Pain and immunity

2021 ◽  
pp. 67-71
Author(s):  
Simon Beggs
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Early Life ◽  
System Development ◽  
Later Life ◽  
Nervous System Development ◽  
Neuronal Function ◽  
Neuronal Homeostasis ◽  
Neuroimmune Interactions ◽  
The Central Nervous System

The central nervous system (CNS) and immune system are inextricably linked. The complexity of their interactions is still being unraveled, but the list of processes mediated wholly or in part by neuroimmune interactions continues to grow. The influence of the immune system is crucial for normal nervous system development both pre- and postnatally, for maintaining neuronal homeostasis in the mature CNS and modulating synaptic plasticity. Aberrations in this crosstalk have been implicated in many neurodevelopmental and psychiatric disorders. It is not feasible to explore neuronal function at any point in the lifespan, in health or disease, without considering the influence of the immune system. In the adult animal it is now well established that pain chronicity is maintained by immune influence upon the neuronal nociceptive system, although, fascinatingly, there is now evidence for a marked sexual dimorphism in how the immune and nervous systems interact. This holds true for pain in early life, where the two still-developing systems provide a very different environment to mediate nociception and pain. Of particular interest is how the immune system and sex interact to early life painful events to prime pain responses in later life.

Basic mechanisms of, and treatment targets for, depressive disorders

2020 ◽  
pp. 779-788
Author(s):  
Marcela Pereira ◽  
Roberto Andreatini ◽  
Per Svenningsson
Keyword(s):  
Major Depressive Disorder ◽  
Immune System ◽  
Depressive Disorder ◽  
Affective Disorders ◽  
Sleep Disturbances ◽  
Depressive Disorders ◽  
Signs And Symptoms ◽  
Molecular Pathways ◽  
Therapy Targets ◽  
Gene Environment

The diagnosis of major depressive disorder (MDD) relies on the presence of a certain number of signs and symptoms, including feelings of guilt, hopelessness, dysphoria, cognitive dysfunction, persistent sleep, and appetite abnormalities. These signs and symptoms overlap with other conditions such as anxiety, bipolar, and seasonal affective disorders. This chapter provides an overview of the basic neurobiological mechanisms underlying MDD and its treatment. There are several alterations in the molecular pathways and neuronal networks associated with MDD. The chapter focuses here on: gene × environment interactions, dysfunctional brain circuitries, neurotransmitter alterations, maladaptation in neurotrophins and neuroplasticity, hypothalamus–pituitary–adrenal (HPA) axis dysfunction, abnormal immune system responses, circadian arrhythmicity, and sleep disturbances. The chapter briefly describes the mechanisms of actions for approved antidepressant therapies and also discusses recent insights into the pathophysiology of MDD and future possible therapy targets.

scholarly journals Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back

2020 ◽  
Vol 21 (12) ◽  
pp. 4448 ◽  
Author(s):  
Osnat Almogi-Hazan ◽  
Reuven Or
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Immune Surveillance ◽  
Endocannabinoid System ◽  
The Other ◽  
Clinical Use ◽  
Medical Cannabis ◽  
Pathological Conditions ◽  
Regulatory Properties

The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.

scholarly journals Role of 5-HT7 receptors in the immune system in health and disease

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Alejandro Quintero-Villegas ◽  
Sergio Iván Valdés-Ferrer
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Blood Platelets ◽  
Pain Tolerance ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Health And Disease

AbstractIn mammalians, serotonin (5-HT) has critical roles in the central nervous system (CNS), including mood stability, pain tolerance, or sleep patterns. However, the vast majority of serotonin is produced by intestinal enterochromaffin cells of the gastrointestinal tract and circulating blood platelets, also acting outside of the CNS. Serotonin effects are mediated through its interaction with 5-HT receptors (5-HTRs), a superfamily with a repertoire of at least fourteen well-characterized members. 5-HT7 receptors are the last 5-HTR member to be identified, with well-defined functions in the nervous, gastrointestinal, and vascular systems. The effects of serotonin on the immune response are less well understood. Mast cells are known to produce serotonin, while T cells, dendritic cells, monocytes, macrophages and microglia express 5-HT7 receptor. Here, we review the known roles of 5-HT7 receptors in the immune system, as well as their potential therapeutic implication in inflammatory and immune-mediated disorders.

The Neuroimmune Interface in Prion Diseases

Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 250-255
Author(s):  
Michael A. Klein ◽  
Adriano Aguzzi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Prion Disease ◽  
Neurodegenerative Disorders ◽  
Prion Diseases ◽  
The Central Nervous System

Prion diseases are fatal neurodegenerative disorders of animals and humans. Here we address the role of the immune system in the spread of prions from peripheral sites to the central nervous system and its potential relevance to iatrogenic prion disease.

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