Glia
Sphingolipids are a class of biologically active lipids that have a role in multiple biological processes including inflammation. Sphingolipids exert their functions by direct signaling or through signaling by their specific receptors. Phosphorylated FTY720 (FTY720P) is a sphingosine 1‐phosphate (S1P) analogue that is currently in trial for treatment of multiple sclerosis (MS), which targets all S1P...
Although there is increasing evidence that blood‐derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is...
In multiple sclerosis (MS), one strategy to reduce disability is enhancement of endogenous repair by remyelinating oligodendrocytes derived from oligodendrocyte progenitor cells (OP). An important prerequisite is determining the abundance of OP relative to oligodendrocytes in normal human central nervous system (CNS), which, in turn, requires reliable OP identification. To achieve this, cat and human...
Oxidative stress has been implicated in the progression of ageing and in many age‐related neurodegenerative conditions. Astrocytes play a major role in the antioxidant protection of the brain, yet little is known about how the antioxidant defenses of astrocytes change across the lifespan. This study assessed the antioxidant capacity and glutathione metabolism of astrocytes cultured from the brains...
Manganese in excess is neurotoxic and causes CNS injury resembling that of Parkinson's disease. In brain, astrocytes predominantly take up and accumulate manganese and are thus vulnerable to its toxicity. Manganese was shown to induce cell swelling in cultured astrocytes, and oxidative/nitrosative stress (ONS) mediates such swelling. As aquaporin‐4 (AQP4) is important in the mechanism of astrocyte...
Increasing evidence suggests that CCN matricellular proteins play important roles in inflammation. One of the major cell types that handle inflammation in the brain is the astrocyte, which, upon activation, dramatically increases its production of cytokines and chemokines. Here, we report that NOV/CCN3, added to primary cultured rat brain astrocytes, markedly increased the expression of CCL2 and CXCL1...
HIV‐1 Tat protein is an important pathogenic factor in HIV‐1‐associated neurological diseases. One hallmark of HIV‐1 infection of the central nervous system (CNS) is astrocytosis, which is characterized by elevated glial fibrillary acidic protein (GFAP) expression in astrocytes. We have shown that Tat activates GFAP expression in astrocytes [Zhou et al., (2004) Mol Cell Neurosci 27:296–305] and that...
Ablation of functional peroxisomes from all neural cells in Nestin‐Pex5 knockout mice caused remarkable neurological abnormalities including motoric and cognitive malfunctioning accompanied by demyelination, axonal degeneration, and gliosis. An oligodendrocyte selective Cnp‐Pex5 knockout mouse model shows a similar pathology, but with later onset and slower progression. Until now, the link between...
While astrocytes produce key inflammatory mediators following exposure to neurotropic nonsegmented negative‐sense RNA viruses such as rabies virus and measles virus, the mechanisms by which resident central nervous system (CNS) cells perceive such viral challenges have not been defined. Recently, several cytosolic DExD/H box RNA helicases including retinoic acid‐inducible gene I (RIG‐I) have been...
The dentate gyrus is a brain region where neurons are continuously born throughout life. In the adult, the role of its radial glia in neurogenesis has attracted much attention over the past years; however, little is known about the generation and differentiation of glial cells and their relationship to radial glia during the ontogenetic development of this brain structure. Here, we combine immunohistochemical...
The nervous system of echinoderms has long been considered too unique to be directly comparable to the nervous system of other Deuterostomia. Using two novel monoclonal antibodies in combination with epifluorescence, confocal, and electron microscopy, we demonstrate here that the central nervous system of the sea cucumber Holothuria glaberrima possesses a major non‐neuronal cell type, which shares...
A number of human immunodeficiency virus type‐1 (HIV) positive subjects are also opiate abusers. These individuals are at high risk to develop neurological complications. However, little is still known about the molecular mechanism(s) linking opiates and HIV neurotoxicity. To learn more, we exposed rat neuronal/glial cultures prepared from different brain areas to opiate agonists and HIV envelope...
The study shows the dynamic expression of connexin47 (Cx47) in oligodendrocytes and myelin of mice, either in myelinogenesis occurring in early development or in an experimental model of new‐myelinogenesis of adult mice. Cx47 first appeared in the embryonic mouse brain at E10.5 successively the expression increased, principally in regions populated by developing oligodendrocytes. The expression declined...
Various models of experimental autoimmune encephalomyelitis (EAE) have led to insights into the pathogenesis and novel therapies for multiple sclerosis. One generalized EAE model uses immunizing the Lewis Rat with myelin oligodendrocyte glycoprotein (MOG) and complete Freund's adjuvant that induces systemic disease and inflammatory lesions at random central nervous system (CNS) locations. These lesions...
Olfactory ensheathing cells (OEC) have the ability to promote regeneration in the nervous system. Hence, they hold promise for cell therapy. Most of the experimental studies have investigated the role of OECs taken from olfactory bulb (OB). However, for a clinical human application, olfactory mucosa (OM) seems to be the only acceptable source for OECs. Many studies have compared the distinct ability...
Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K+–Cl− cotransporter (KCC) family includes four isoforms (KCC1–4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K+ and Cl− with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results...
The purpose of this study was to ascertain the relative contribution of neural stem/progenitor cells (NSPCs) of the subventricular zone (SVZ) to lineages that repopulate the injured striatum following focal ischemia. We utilized a tamoxifen‐inducible Cre/loxP system under control of the nestin promoter, which provides permanent YFP labeling of multipotent nestin+ SVZ‐NSPCs prior to ischemic injury...
Neuron/glial 2 (NG2)‐expressing cells are often referred to as oligodendrocyte precursor cells. NG2‐expressing cells have also been identified as multipotent progenitor cells. However, microglia‐like NG2 glial cells have not been fully examined in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, we chose two rat models of PD, i.e., intranigral or intrastriatal injection...
The most common cause of Pelizaeus‐Merzbacher (PMD) is due to duplication of the PLP1 gene but it is unclear how increased gene dosage affects PLP turnover and causes dysmyelination. We have studied the dynamics of PLP/DM20 in a transgenic mouse model of PMD with increased gene dosage of the proteolipid protein gene (Plp1). The turnover of PLP/DM20 were investigated using an ex‐vivo brain slice system...
Microglia respond rapidly to injury, increasing their synthesis and release of inflammatory mediators, many of which contribute to the maintenance of persistent pain following CNS or PNS injury. We have recently shown that the lysosomal cysteine protease Cathepsin S (CatS) expressed by spinal microglia is vital for the full expression of neuropathic pain. Here we evaluated the mechanisms by which...