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The p38 mitogen‐activated protein kinases (p38 MAPKs) are a family of kinases that regulate a number of cellular functions including cell migration, proliferation, and differentiation. We have previously reported a role for p38 MAPK in the regulation of oligodendrocyte (OLG) differentiation and Schwann cell myelination. Here, we extend our previous findings by showing that a p38 substrate, mitogen‐activated...
The system x (Sx) transporter functions to mediate the exchange of extracellular cystine (L‐Cys2) and intracellular glutamate (L‐Glu). Internalized L‐Cys2 serves as a rate‐limiting precursor for the biosynthesis of glutathione (GSH), while the externalized L‐Glu can contribute to either excitatory signaling or excitotoxicity. In the present study the influence of culture conditions (with and...
Astrocytes have an important role in the regulation of inflammation within the central nervous system (CNS). In neuroinflammatory conditions such as multiple sclerosis, numerous cytokines and chemokines are elevated including IL‐6, IL‐17, and CCL20. IL‐17 enhances IL‐6 signaling and subsequent IL‐6 expression in astrocytes. CCL20 is a CC motif chemokine that functions as a chemoattractant to facilitate...
The concentration of the excitotoxic amino acid, L‐glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood‐brain barrier endothelium in brain L‐glutamate homeostasis. Transendothelial transport‐ and accumulation studies of 3H‐L‐glutamate, 3H‐L‐aspartate, and...
Type I interferons (IFNα/β) provide a primary defense against infection. Nevertheless, the dynamics of IFNα/β induction and responsiveness by central nervous system (CNS) resident cells in vivo in response to viral infections are poorly understood. Mice were infected with a neurotropic coronavirus with tropism for oligodendroglia and microglia to probe innate antiviral responses during acute encephalomyelitis...
Signaling via the major excitatory amino acid glutamate has been implicated in the regulation of various aspects of the biology of oligodendrocytes, the myelinating cells of the central nervous system (CNS). In this respect, cells of the oligodendrocyte lineage have been described to express a variety of glutamate‐responsive transmembrane proteins including sodium‐dependent glutamate transporters...
Astrocytes produce and export the antioxidant glutathione (GSH). Previously, we found that interleukin‐1β (IL‐1β) enhanced the expression of astrocyte system xc−, the transporter that delivers the rate‐limiting substrate for GSH synthesis—cyst(e)ine. Herein, we demonstrate directly that IL‐1β mediates a time‐dependent increase in extracellular GSH levels in cortical astrocyte cultures, suggesting...
Blood–brain barrier (BBB) characteristics are induced and maintained by crosstalk between brain microvascular endothelial cells and neighboring cells. Using in vitro cell models, we previously found that a bystander effect was a cause for Japanese encephalitis‐associated endothelial barrier disruption. Brain astrocytes, which neighbor BBB endothelial cells, play roles in the maintenance of BBB integrity...
During central nervous system development, oligodendrocyte progenitors (OLPs) establish multiple branched processes and axonal contacts to initiate myelination. A complete understanding of the molecular signals implicated in cell surface interaction to initiate myelination/remyelination is currently lacking. The objective of our study was to assess whether Cdon, a cell surface protein that was shown...
Under steady‐state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c‐eYFP mice. We previously showed that these mice carry the Crb1rd8 mutation, which causes retinal dystrophic lesions; therefore...
The “shock and kill” HIV‐1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency‐reversing agents (LRAs). Although resting CD4+ T cells latently infected with HIV‐1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration...
The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II+ cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined...
The presence of peripheral myelinating cells in the central nervous system (CNS) has gained the neurobiologist attention over the years. Despite the confirmed presence of Schwann cells in the CNS in pathological conditions, and the long list of their beneficial effects on central remyelination, the cues that impede or allow Schwann cells to successfully conquer and remyelinate central axons remain...
Since the introduction of the combined antiretroviral therapy, HIV‐1 infection has become a manageable chronic disease in which patients display a life expectancy almost identical to the general population. Nevertheless, various age‐related pathologies such as neurocognitive disorders have emerged as serious complications. A “shock and kill” strategy using latency‐reversing agents (LRA) to reactivate...
The crosstalk between glial cells and neurons represents an exceptional feature for maintaining the normal function of the central nervous system (CNS). Increasing evidence has revealed the importance of glial progenitor cells in adult neurogenesis, reestablishment of cellular pools, neuroregeneration, and axonal (re)myelination. Several types of glial progenitors have been described, as well as...
Addition of arginine (Arg) from tRNA can cause major alterations of structure and function of protein substrates. This post‐translational modification, termed protein arginylation, is mediated by the enzyme arginyl‐tRNA‐protein transferase 1 (Ate1). Arginylation plays essential roles in a variety of cellular processes, including cell migration, apoptosis, and cytoskeletal organization. Ate1 is associated...
Mechanisms regulating oligodendrocyte differentiation, developmental myelination and myelin maintenance in adulthood are complex and still not completely described. Their understanding is crucial for the development of new protective or therapeutic strategies in demyelinating pathologies such as multiple sclerosis. In this perspective, we have investigated the role of Cyclin‐dependent kinase 7 (Cdk7),...
Prion diseases are transmissible, neurodegenerative disorders associated with misfolding of the prion protein. Previous studies show that reduction of microglia accelerates central nervous system (CNS) prion disease and increases the accumulation of prions in the brain, suggesting that microglia provide neuroprotection by phagocytosing and destroying prions. In Csf1rΔFIRE mice, the deletion of an...
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