Glia
Cells of the oligodendrocyte lineage, which form the myelinating glia of the vertebrate central nervous system, undergo a stepwise developmental progression entailing specification from neuroepithelial precursors, proliferation, migration to expand and distribute the population, and differentiation to ensheath axons with myelin. Understanding the genetic mechanisms that regulate each of these steps...
Notch1 receptor signaling regulates oligodendrocyte progenitor differentiation and myelin formation in development, and during remyelination in the adult CNS. In active multiple sclerosis lesions, Notch1 localizes to oligodendrocyte lineage cells, and its ligand Jagged1 is expressed by reactive astrocytes. Here, we examined induction of Jagged1 in human astrocytes, and its impact on oligodendrocyte...
Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of β‐amyloid (Aβ) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Aβ and Aβ deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a...
By promoting cell proliferation, survival and maturation insulin‐like growth factor (IGF)‐I is essential to the normal growth and development of the central nervous system. It is clear that IGF‐I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)‐Akt kinases and MAP kinases signal many of IGF‐I‐IGF1R actions in neural cells, including oligodendrocyte...
CB1 and CB2 receptors are activated by a plethora of cannabinoid compounds, be they endogenously‐produced, plant‐derived or synthetic. These receptors are expressed by microglia, astrocytes and astrocytomas, and their activation regulates these cells' differentiation, functions and viability. Recent studies show that glial cells also express cannabinoid‐like receptors, and that their activation regulates...
According to previously published ultrastructural studies, oligodendrocytes in white matter exhibit gap junctions with astrocytes, but not among each other, while in vitro oligodendrocytes form functional gap junctions. We have studied functional coupling among oligodendrocytes in acute slices of postnatal mouse corpus callosum. By whole‐cell patch clamp we dialyzed oligodendrocytes with biocytin,...
The unravelling of the polarized distribution of AQP4 in perivascular astrocytic endfeet has revitalized the interest in the role of astrocytes in controlling water and ion exchange at the brain–blood interface. The importance of the endfeet is based on the premise that they constitute a complete coverage of the vessel wall. Despite a number of studies based on different microscopic techniques this...
The glycine transporter 1 (GlyT1) is expressed in astrocytes and selected neurons of the mammalian CNS. In newborn mice, GlyT1 is crucial for efficient termination of glycine‐mediated inhibitory neurotransmission. Furthermore, GlyT1 has been implicated in the regulation of excitatory N‐methyl‐D‐asparate (NMDA) receptors. To evaluate whether glial and neuronal GlyT1 have distinct roles at inhibitory...
Human bone marrow‐derived mesenchymal stem cells (hMSCs) are considered a desirable cell source for autologous cell transplantation therapy to treat nervous system injury due to their ability to differentiate into specific cell types and render the tissue microenvironment more favorable for tissue repair by secreting various growth factors. To potentiate their possible trophic effect, hMSCs were induced...
Bone marrow stromal cells (BMSCs) facilitate functional recovery in rats after focal ischemic attack. Growing evidence suggests that the secretion of various bioactive factors underlies BMSCs' beneficial effects. This study investigates the expression of glial cell derived neurotrophic factor (GDNF) in the ischemic hemisphere with or without BMSC administration. Adult male Wistar rats were subjected...
To understand the pathomechanisms of spinal cord injuries will be a prerequisite to develop efficient therapies. By investigating acute lesions of spinal cord white matter in anesthetized mice with fluorescently labeled microglia and axons using in vivo two‐photon laser‐scanning microscopy (2P‐LSM), we identified the messenger nitric oxide (NO) as a modulator of injury‐activated microglia. Local tissue...
Glial progenitors in the white matter and the subventricular zone are the major population of cycling cells in the postnatal central nervous system, and thought to be candidates for glioma‐initiating cells. However, less is known about the dividing cell populations in the brainstem than those in the cerebrum, leading to the lag of basic understanding of brainstem gliomas. We herein demonstrate much...
Brief forebrain ischemia is a model of the delayed hippocampal neuronal loss seen in patients following cardiac arrest and resuscitation. Previous studies demonstrated that selective dysfunction of hippocampal CA1 subregion astrocytes occurs hours to days before delayed neuronal death. In this study we tested the strategy of directing protection to astrocytes to protect neighboring neurons from forebrain...
Elevated levels of Oncostatin M (OSM), an interleukin‐6 family cytokine, have been observed in multiple sclerosis (MS), HIV‐associated neurocognitive disorder (HAND), and glioblastoma (GBM); however, its effects within the CNS are not well understood. OSM regulates gene expression primarily by activating the JAK/STAT, NF‐κB, and/or MAPK pathways, in a cell‐type specific manner. In our studies, OSM...
Intracerebral accumulation of amyloid‐β (Aβ) leading to Aβ plaque formation, is the main hallmark of Alzheimer's disease and might be caused by defective Aβ‐clearance. We previously found primary human astrocytes and microglia able to bind and ingest Aβ1‐42 in vitro, which appeared to be limited by Aβ1‐42 fibril formation. We now confirm that astrocytic Aβ‐uptake depends on size and/or composition...
Neuroglobin (Ngb) is proposed to be a neuron‐specific, hypoxia‐responsive, neuroprotective protein. However, results are conflicting concerning both Ngb's physiological and pathological significance. This study was designed to investigate the in vivo localization and regulation of Ngb in different neuropathological models representing traumatic injury, infectious, autoimmune, and excitotoxic pathogeneses...
Glucocorticoids are potent regulators of inflammation exerting permissive, stimulatory, and suppressive effects. Glucocorticoid access to intracellular receptors is regulated by the activity of two distinct enzymes known as 11β‐hydroxysteroid dehydrogenase (11βHSD) Type 1 and Type 2, which catalyze the activation or deactivation of glucocorticoids. Although expression of these enzymes in major organ...
Cerebral hypoxia induces a profound angiogenic response in the central nervous system (CNS). Using a mouse model of chronic cerebral hypoxia, we previously demonstrated that angiogenic vessels in the hypoxic CNS show marked upregulation of the extracellular matrix (ECM) protein fibronectin, along with increased expression of its major receptor, α5β1 integrin on brain endothelial cells (BEC). As cerebral...
Cellular zinc plays a key role in lysosomal change and cell death in neurons and astrocytes under oxidative stress. Here, using astrocytes lacking metallothionein‐3 (MT3), a potential source of labile zinc in the brain, we studied the role of MT3 in oxidative stress responses. H2O2 induced a large increase in labile zinc in wild‐type (WT) astrocytes, but stimulated only a modest rise in MT3‐null astrocytes...
Vascular/parenchymal crosstalk is increasingly recognized as important in the development and maintenance of healthy vascularized tissues. The retina is an excellent model in which to study the role of cell type‐specific contributions to the process of blood vessel and neuronal growth. During retinal vascular development, glial cells such as astrocytes provide the template over which endothelial cells...