scholarly journals The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

2020 ◽  
Vol 18 (5) ◽  
pp. 408-430 ◽  
Author(s):  
Katarzyna Chamera ◽  
Ewa Trojan ◽  
Magdalena Szuster-Głuszczak ◽  
Agnieszka Basta-Kaim

: The bidirectional communication between neurons and microglia is fundamental for the proper functioning of the central nervous system (CNS). Chemokines and clusters of differentiation (CD) along with their receptors represent ligand-receptor signalling that is uniquely important for neuron – microglia communication. Among these molecules, CX3CL1 (fractalkine) and CD200 (OX-2 membrane glycoprotein) come to the fore because of their cell-type-specific localization. They are principally expressed by neurons when their receptors, CX3CR1 and CD200R, respectively, are predominantly present on the microglia, resulting in the specific axis which maintains the CNS homeostasis. Disruptions to this balance are suggested as contributors or even the basis for many neurological diseases. : In this review, we discuss the roles of CX3CL1, CD200 and their receptors in both physiological and pathological processes within the CNS. We want to underline the critical involvement of these molecules in controlling neuron – microglia communication, noting that dysfunctions in their interactions constitute a key factor in severe neurological diseases, such as schizophrenia, depression and neurodegeneration-based conditions.

ISRN Virology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Joséphine M. Reynaud ◽  
Branka Horvat

Human herpesvirus (HHV-) 6A and HHV-6B are two distinct β-herpesviruses which have been associated with various neurological diseases, including encephalitis, meningitis, epilepsy, and multiple sclerosis. Although the reactivation of both viruses is recognized as the cause of some neurological complications in conditions of immunosuppression, their involvement in neuroinflammatory diseases in immunocompetent people is still unclear, and the mechanisms involved have not been completely elucidated. Here, we review the available data providing evidence for the capacity of HHV-6A and -6B to infect the central nervous system and to induce proinflammatory responses by infected cells. We discuss the potential role of both viruses in neuroinflammatory pathologies and the mechanisms which could explain virus-induced neuropathogenesis.


2020 ◽  
Vol 26 (4) ◽  
pp. 449-453
Author(s):  
Jacob A. Kahn ◽  
Jeffrey T. Waltz ◽  
Ramin M. Eskandari ◽  
Cynthia T. Welsh ◽  
Michael U. Antonucci

The authors report an unusual presentation of juvenile xanthogranuloma (JXG), a non–Langerhans cell histiocytosis of infancy and early childhood. This entity typically presents as a cutaneous head or neck nodule but can manifest with more systemic involvement including in the central nervous system. However, currently there is limited information regarding specific imaging features differentiating JXG from other neuropathological entities, with diagnosis typically made only after tissue sampling. The authors reviewed the initial images of a young patient with shunt-treated hydrocephalus and enlarging, chronic, extraaxial processes presumed to reflect subdural collections from overshunting, and they examine the operative discovery of a mass lesion that was pathologically proven to be JXG. Their results incorporate the important associated histological and advanced imaging features, including previously unreported metabolic activity on FDG PET. Ultimately, the case underscores the need to consider JXG in differential diagnoses of pediatric intracranial masses and highlights the potential role of PET in the initial diagnosis and response to treatment.


2020 ◽  
Vol 18 ◽  
Author(s):  
Lingdi Nie ◽  
Wen-Rui Ye ◽  
Shangbin Chen ◽  
Domenico Chirchiglia ◽  
Minyan Wang

: Src family kinases (SFK) are a group of non-receptor tyrosine kinases which play a pivotal role in cellular responses and oncogenesis. Accumulating evidence suggest that SFK also act as a key component in signalling pathways of the central nervous system (CNS) in both physiological and pathological conditions. Despite the crucial role of SFK in signal transduction of the CNS, the relationship between SFK and molecules implicated in pain has been relatively unexplored. This article briefly reviews the recent advances uncovering the interplay of SFK with diverse membrane proteins and intracellular proteins in the CNS and the importance of SFK in the pathophysiology of migraine and neuropathic pain. Mechanisms underlying the role of SFK in these conditions and potential clinical applications of SFK inhibitors in neurological diseases are also summarised. We propose that SFK are the convergent point of signalling pathways in migraine and neuropathic pain and may constitute a promising therapeutic target for these diseases.


2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.


Author(s):  
Lingyi Huang ◽  
Zizhuo Zheng ◽  
Ding Bai ◽  
Xianglong Han

Abstract: Stem cells from human exfoliated deciduous teeth (SHEDs) are relatively easy to isolate from exfoliated deciduous teeth, which are obtained via dental therapy as biological waste. SHEDs originate from the embryonic neural crest and therefore have considerable potential for neurogenic differentiation. Currently, an increasing amount of research attention is focused on the therapeutic applications of SHEDs in neurological diseases and injuries. In this article, we summarize the biological characteristics of SHEDs and the potential role of SHEDs and their derivatives, including conditioned medium from SHEDs and the exosomes they secrete, in the prevention and treatment of neurological diseases and injuries.


Author(s):  
Yang Du ◽  
Lei Chen ◽  
Xue-Song Li ◽  
Xiao-Lin Li ◽  
Xiang-Dong Xu ◽  
...  

Abstract Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.


2019 ◽  
Vol 11 (3) ◽  
pp. 709-723 ◽  
Author(s):  
Kan Gao ◽  
Chun-long Mu ◽  
Aitak Farzi ◽  
Wei-yun Zhu

ABSTRACT The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Subhajit Das Sarma ◽  
Koushik Chatterjee ◽  
Himadri Dinda ◽  
Dhriti Chatterjee ◽  
Jayasri Das Sarma

Microglia is one of the major resident immune cells in the central nervous system and is considered to be the key cellular mediator of neuroinflammatory processes. Identification of different Microglial states of activation by morphologic means has been one of the major challenges in the field of neurobiology of diseases. Therefore, microglial biology demands techniques to identify differing stages of microglia in different neuroanatomic locations as well as understanding the role of Microglia in different Neurological diseases. This present study is aimed towards summarizing the literature and for understanding the progress made in different Cytomorphological and Cytochemical techniques of identifying Microglia. This study also review recently used Immunohistochemistry techniques, along with Ultrastructural studies determining different morphological features of resting to activated phagocytic Microglia in a viral induced experimental animal model of neuroinflammation. Results revealed that chronic Microglial activation is considered to be an important component of neuronal dysfunction, injury, and loss (and hence to disease progression). Thus, Microglial research with special emphasis on identification of different activation states of Microglia has gradually become significant.


2014 ◽  
Vol 10 (01) ◽  
pp. 48
Author(s):  
Dionysis Papadatos-Pastos ◽  
James Hall ◽  
Ruth Pettengell ◽  
Leslie R Bridges ◽  
Barry Newell ◽  
...  

We present a case of a 64-year-old man who was diagnosed with a primary anaplastic large cell lymphoma of the central nervous system (PCNSAL). He had received radical chemotherapy and radiotherapy for a non-small cell lung cancer (NSCLC) in the past. There is no known association between NSCLC and PCNSAL. We describe the diagnostic and therapeutic challenges associated with these rare intracranial lymphomas and highlight the potential role of newer biological agents in patients with anaplastic lymphoma kinase (ALK-1) positive PCNSAL.


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