Glia
Toll‐like receptors comprise a family of evolutionary conserved pattern recognition receptors that act as a first defense line in the innate immune system. Upon stimulation with microbial ligands, they orchestrate the induction of a host defense response by activating different signaling cascades. Interestingly, they appear to detect the presence of endogenous signals of danger as well and as such,...
Semaphorin 7A (Sema7A) is involved in the formation of the central nervous system during development by operating axon guidance and neuronal migration. We investigated the expression of the TGFβ‐inducible Sema7A following spinal cord injury (SCI). After SCI, Sema7A+ cells accumulated specifically in lesion areas resulting in significantly enhanced Sema7A expression at the injury site (P < 0.0001)...
In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting...
Microglial cells (MCs) are active sensors and reactive phagocytes of neural tissues. They are known to migrate and accumulate in areas of neuronal damage. Thus, microglial locomotion is an essential feature of the inflammatory reaction in neural tissue. Yet, to our knowledge there has been no report of direct in vivo observation of the migration of MCs. Here, we show that intravitreally injected cyanine...
A common pathway underlying a variety of neurodegenerative disorders is the aggregation and deposition of misfolded proteins. Proteasomal inhibition has been demonstrated to promote the formation of intracellular inclusions. We have shown before that astrocytes respond to the treatment with the proteasome inhibitor MG‐132 by aggresome formation and cytoskeletal disturbances, but unlike oligodendrocytes...
Nucleotides and nucleosides play important roles by maintaining brain homeostasis, and their extracellular concentrations are mainly regulated by ectonucleotidases and nucleoside transporters expressed by astrocytes. Extracellularly applied NAD+ prevents astrocyte death caused by excessive activation of poly(ADP‐ribose) polymerase‐1, of which the molecular mechanism has not been fully elucidated....
Heavy marijuana use has been linked to white matter histological alterations. However, the impact of cannabis constituents on oligodendroglial pathophysiology remains poorly understood. Here, we investigated the in vitro effects of cannabidiol, the main nonpsychoactive marijuana component, on oligodendrocytes. Exposure to cannabidiol induced an intracellular Ca2+ rise in optic nerve oligodendrocytes...
Previously, we and others documented that statins including‐lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a...
Nitric oxide (NO) has been long recognized as an atypical neuronal messenger affecting excitatory synaptic transmission, but its cellular source has remained unresolved as the neuronal isoform of NO synthase (nNOS) in many brain regions is expressed only by small subsets of inhibitory neurons. It is generally believed that the glial NO‐producing isoform (iNOS) is not expressed in the normal brain,...
TGR5 (Gpbar‐1) is a membrane‐bound bile acid receptor in the gastrointestinal tract and immune cells with pleiotropic actions. As shown in the present study, TGR5 is also expressed in astrocytes and neurons. Here, TGR5 may act as a neurosteroid receptor, which is activated by nanomolar concentrations of 5β‐pregnan‐3α‐ol‐20‐one and micromolar concentrations of 5β‐pregnan‐3α‐17α‐21‐triol‐20‐one and...
The mechanisms underlying neuropathic pain are poorly understood. However, several studies have implied a role for reactive microglia located in the dorsal horn in neuropathic pain. To clarify the roles of activated microglia in neuropathic pain, we investigated the interactions among microglia and other neural components in the dorsal horn using electron microscopy. Microglia were more abundantly...
Intracerebral hemorrhage (ICH) induces neurovascular injury via poorly defined mechanisms. The aim of this study was to determine whether gliovascular communication may restrict hemorrhagic vascular injury. Hemin, a hemoglobin by‐product, concentration‐ and time‐dependently increased apoptotic cell death in mouse bEnd.3 cells and in primary human brain microvascular endothelial cells, at least in...
We investigated the neuroprotective effect of glucosamine (GlcN) in a rat middle cerebral artery occlusion model. At the highest dose used, intraperitoneal GlcN reduced infarct volume to 14.3% ± 7.4% that of untreated controls and afforded a reduction in motor impairment and neurological deficits. Neuroprotective effects were not reproduced by other amine sugars or acetylated‐GlcN, and GlcN suppressed...
Purpose:Human remyelination promoting IgM mAbs target oligodendrocytes (OLs) and function in animal models of multiple sclerosis (MS). However, their mechanism of action is unknown. This study seeks to identify the cellular mechanism of action of a recombinant human IgM on OL survival.
Methods:Binding of rHIgM22 to the surface of rat OLs was studied by co‐localization with various markers. RHIgM22‐mediated...
Oligodendrocyte lineage cells are susceptible to a variety of insults including hypoxia, excitotoxicity, and reactive oxygen species. Demyelination is a well‐recognized feature of several CNS disorders including multiple sclerosis, white matter strokes, progressive multifocal leukoencephalopathy, and disorders due to mitochondrial DNA mutations. Although mitochondria have been implicated in the demise...
Experimental autoimmune encephalomyelitis (EAE) is a T cell‐mediated neuroinflammatory disease that is often used as a model of multiple sclerosis. EAE can follow either relapsing‐remitting (RR) or chronic (CH) courses, yet the factors responsible for differentially inducing these forms of disease remain largely unknown. Proinflammatory cytokines play an important role in EAE, and signaling by these...
Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions...
We recently demonstrated that interleukin‐1β (IL‐1β) increases system xc− (cystine/glutamate antiporter) activity in mixed cortical cell cultures, resulting in an increase in hypoxic neuronal injury when glutamate clearance is impaired. Herein, we demonstrate that neurons, astrocytes, and microglia all express system xc− subunits (xCT, 4F2hc, RBAT) and are capable of cystine import. However, IL‐1β...
Accumulating evidence suggests that spinal astrocytes play an important role in the genesis of persistent pain, by increasing the activity of spinal cord nociceptive neurons, i.e., central sensitization. However, direct evidence of whether activation of astrocytes is sufficient to induce chronic pain symptoms is lacking. We investigated whether and how spinal injection of activated astrocytes could...
Macrophages play an important role in demyelination in multiple sclerosis (MS). Activated macrophages ingest myelin particles, thereby acquiring a foamy appearance. Foamy macrophages in MS lesions were described as being anti‐inflammatory. Therefore, these cells might play a role in modulating the inflammatory state of an active lesion. Here, we investigated the mechanism by which myelin uptake leads...