Cytokines and Cytokine Receptors in Brain Homeostasis

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 7946

Special Issue Editors


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Guest Editor
Department of Biomedical Sciences, University of Milan, 20122 Milan, Italy
Interests: neuropathology; brain diseases; neurobiology

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Guest Editor
Department of Molecular Animal Physiology, Radboud University Nijmegen, Nijmegen, The Netherlands
Interests: molecular and cellular neurobiology

Special Issue Information

Dear Colleagues,

Since the first identification of cytokines and growth factors, the literature on this topic has expanded enormously, yet many questions remain, e.g., where and how these molecules play a role in the normal growth and differentiation of tissues and/or cells, such as central nervous system (CNS) cells, immune-committed cells, and neoplastic cells.

Cytokines and growth factors are produced by all CNS cell types and play key roles in the proliferation and differentiation of neural stem cells, oligodendrocytes, astrocytes and microglia, myelin production and maintenance, and synaptic transmission. There is also a growing awareness that vitamins positively or negatively modulate the synthesis of some cytokines and growth factors in the CNS. CNS cytokines and growth factors are essential for CNS–immune system and CNS–hormone system communications. Furthermore, research on the mechanisms of signaling transmission pathways, i.e., the post-receptor mechanisms of action, of cytokines and growth factors has continued to grow quite rapidly. Lastly, the roles of these molecules in the different aspects of the pathogenesis of some CNS diseases (whether demyelinating or not) have been extensively investigated, although we still know very little about this topic.

This Special Issue examines some of the aforementioned aspects and, as a whole, gives a broad survey of the state of the art in this exciting field. We think that the topic of this Special Issue will be of particular interest not only to neurologists and neurobiologists but also to physicians and specialists in various areas of medicine.

Prof. Dr. Giuseppe Scalabrino
Dr. Gerard Martens
Guest Editors

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Keywords

  • EGF
  • oligodendrocytes
  • multiple sclerosis
  • experimental CNS demyelinating diseases
  • CNS myelin

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Published Papers (2 papers)

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Research

32 pages, 9278 KiB  
Article
Molecular Signature of Neuroinflammation Induced in Cytokine-Stimulated Human Cortical Spheroids
by Kim M. A. De Kleijn, Kirsten R. Straasheijm, Wieteke A. Zuure and Gerard J. M. Martens
Biomedicines 2022, 10(5), 1025; https://doi.org/10.3390/biomedicines10051025 - 29 Apr 2022
Cited by 2 | Viewed by 3283
Abstract
Crucial in the pathogenesis of neurodegenerative diseases is the process of neuroinflammation that is often linked to the pro-inflammatory cytokines Tumor necrosis factor alpha (TNFα) and Interleukin-1beta (IL-1β). Human cortical spheroids (hCSs) constitute a valuable tool to study the molecular mechanisms underlying neurological [...] Read more.
Crucial in the pathogenesis of neurodegenerative diseases is the process of neuroinflammation that is often linked to the pro-inflammatory cytokines Tumor necrosis factor alpha (TNFα) and Interleukin-1beta (IL-1β). Human cortical spheroids (hCSs) constitute a valuable tool to study the molecular mechanisms underlying neurological diseases in a complex three-dimensional context. We recently designed a protocol to generate hCSs comprising all major brain cell types. Here we stimulate these hCSs for three time periods with TNFα and with IL-1β. Transcriptomic analysis reveals that the main process induced in the TNFα- as well as in the IL-1β-stimulated hCSs is neuroinflammation. Central in the neuroinflammatory response are endothelial cells, microglia and astrocytes, and dysregulated genes encoding cytokines, chemokines and their receptors, and downstream NFκB- and STAT-pathway components. Furthermore, we observe sets of neuroinflammation-related genes that are specifically modulated in the TNFα-stimulated and in the IL-1β-stimulated hCSs. Together, our results help to molecularly understand human neuroinflammation and thus a key mechanism of neurodegeneration. Full article
(This article belongs to the Special Issue Cytokines and Cytokine Receptors in Brain Homeostasis)
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9 pages, 1217 KiB  
Article
Pitavastatin Ameliorates Lipopolysaccharide-Induced Blood-Brain Barrier Dysfunction
by Takashi Fujimoto, Yoichi Morofuji, Andrej Kovac, Michelle A. Erickson, Mária A. Deli, Masami Niwa and William A. Banks
Biomedicines 2021, 9(7), 837; https://doi.org/10.3390/biomedicines9070837 - 18 Jul 2021
Cited by 8 | Viewed by 3807
Abstract
Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood–brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse [...] Read more.
Statins have neuroprotective effects on neurological diseases, including a pleiotropic effect possibly related to blood–brain barrier (BBB) function. In this study, we investigated the effects of pitavastatin (PTV) on lipopolysaccharide (LPS)-induced BBB dysfunction in an in vitro BBB model comprising cocultured primary mouse brain endothelial cells, pericytes, and astrocytes. LPS (1 ng/mL, 24 h) increased the permeability and lowered the transendothelial electrical resistance of the BBB, and the co-administration of PTV prevented these effects. LPS increased the release of interleukin-6, granulocyte colony-stimulating factor, keratinocyte-derived chemokine, monocyte chemotactic protein-1, and regulated on activation, normal T-cell expressed and secreted from the BBB model. PTV inhibited the LPS-induced release of these cytokines. These results suggest that PTV can ameliorate LPS-induced BBB dysfunction, and these effects might be mediated through the inhibition of LPS-induced cytokine production. Clinically, therapeutic approaches using statins combined with novel strategies need to be designed. Our present finding sheds light on the pharmacological significance of statins in the treatment of central nervous system diseases. Full article
(This article belongs to the Special Issue Cytokines and Cytokine Receptors in Brain Homeostasis)
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