Different Types Of Glial Cells Research Articles

Erythropoietin and glial cells in central and peripheral nervous systems.

Erythropoietin (EPO) is the main hematopoietic growth factor prescribed to overcome anemia. It is also a neuroprotective agent. EPO binds to the erythropoietin receptor (EPOR), expressed on neurons and glial cells in the central nervous system (CNS), and exerts its neuroprotective potencies through the EPO-EPOR complex. The mechanism of the signal transduction pathways of EPO on glial cells is defined. EPO-EPOR complex can affect neurological disorders, such as Alzheimer's disease, Parkinson's disease, ischemia, retinal injury, stroke, hypoxia, trauma, and demyelinating diseases, through acting downstream signaling pathways. This review focuses on the roles of EPO in different types of glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells) and their relationships with signaling pathways. Information on the non-erythropoietic action of EPO and related signaling systems in connection with glial cells could enhance EPO treatment to restore different CNS disorders and propose new perspectives on the neuroprotective potential of EPO.

Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma.

Elevation of intraocular pressure (IOP) is a major risk factor for neurodegeneration in glaucoma. Glial cells, which play an important role in normal functioning of retinal neurons, are well involved into retinal ganglion cell (RGC) degeneration in experimental glaucoma animal models generated by elevated IOP. In response to elevated IOP, mGluR I is first activated and Kir4.1 channels are subsequently inhibited, which leads to the activation of Müller cells. Müller cell activation is followed by a complex process, including proliferation, release of inflammatory and growth factors (gliosis). Gliosis is further regulated by several factors. Activated Müller cells contribute to RGC degeneration through generating glutamate receptor-mediated excitotoxicity, releasing cytotoxic factors and inducing microglia activation. Elevated IOP activates microglia, and following morphological and functional changes, these cells, as resident immune cells in the retina, show adaptive immune responses, including an enhanced release of pro-inflammatory factors (tumor neurosis factor-α, interleukins, etc.). These ATP and Toll-like receptor-mediated responses are further regulated by heat shock proteins, CD200R, chemokine receptors, and metabotropic purinergic receptors, may aggravate RGC loss. In the optic nerve head, astrogliosis is initiated and regulated by a complex reaction process, including purines, transmitters, chemokines, growth factors and cytokines, which contributes to RGC axon injury through releasing pro-inflammatory factors and changing extracellular matrix in glaucoma. The effects of activated glial cells on RGCs are further modified by the interplay among different types of glial cells. This review is concluded by presenting an in-depth discussion of possible research directions in this field in the future.

Glial Cells and Brain Diseases: Inflammasomes as Relevant Pathological Entities.

Inflammation mediated by the innate immune system is a physiopathological response to diverse detrimental circumstances such as microbe infections or tissular damage. The molecular events that underlie this response involve the assembly of multiprotein complexes known as inflammasomes. These assemblages are essentially formed by a stressor-sensing protein, an adapter protein and a non-apoptotic caspase (1 or 11). The coordinated aggregation of these components mediates the processing and release of pro-inflammatory interleukins (IL-β and IL-18) and cellular death by pyroptosis induction. The inflammatory response is essential for the defense of the organism; for example, it triggers tissue repair and the destruction of pathogen microbe infections. However, when inflammation is activated chronically, it promotes diverse pathologies in the lung, liver, brain and other organs. The nervous system is one of the main tissues where the inflammatory process has been characterized, and its implications in health and disease are starting to be understood. Thus, the regulation of inflammasomes in specific cellular types of the central nervous system needs to be thoroughly understood to innovate treatments for diverse pathologies. In this review, the presence and participation of inflammasomes in pathological conditions in different types of glial cells will be discussed.

Reactive astrocyte-driven epileptogenesis is induced by microglia initially activated following status epilepticus.

Extensive activation of glial cells during a latent period has been well documented in various animal models of epilepsy. However, it remains unclear whether activated glial cells contribute to epileptogenesis, i.e., the chronically persistent process leading to epilepsy. Particularly, it is not clear whether interglial communication between different types of glial cells contributes to epileptogenesis, because past literature has mainly focused on one type of glial cell. Here, we show that temporally distinct activation profiles of microglia and astrocytes collaboratively contributed to epileptogenesis in a drug-induced status epilepticus model. We found that reactive microglia appeared first, followed by reactive astrocytes and increased susceptibility to seizures. Reactive astrocytes exhibited larger Ca2+ signals mediated by IP3R2, whereas deletion of this type of Ca2+ signaling reduced seizure susceptibility after status epilepticus. Immediate, but not late, pharmacological inhibition of microglial activation prevented subsequent reactive astrocytes, aberrant astrocyte Ca2+ signaling, and the enhanced seizure susceptibility. These findings indicate that the sequential activation of glial cells constituted a cause of epileptogenesis after status epilepticus. Thus, our findings suggest that the therapeutic target to prevent epilepsy after status epilepticus should be shifted from microglia (early phase) to astrocytes (late phase).

Cell specific quantitative iron mapping on brain slices by immuno-\xb5PIXE in healthy elderly and Parkinson\u2019s disease

Iron is essential for neurons and glial cells, playing key roles in neurotransmitter synthesis, energy production and myelination. In contrast, high concentrations of free iron can be detrimental and contribute to neurodegeneration, through promotion of oxidative stress. Particularly in Parkinson’s disease (PD) changes in iron concentrations in the substantia nigra (SN) was suggested to play a key role in degeneration of dopaminergic neurons in nigrosome 1. However, the cellular iron pathways and the mechanisms of the pathogenic role of iron in PD are not well understood, mainly due to the lack of quantitative analytical techniques for iron quantification with subcellular resolution. Here, we quantified cellular iron concentrations and subcellular iron distributions in dopaminergic neurons and different types of glial cells in the SN both in brains of PD patients and in non-neurodegenerative control brains (Co). To this end, we combined spatially resolved quantitative element mapping using micro particle induced X-ray emission (µPIXE) with nickel-enhanced immunocytochemical detection of cell type-specific antigens allowing to allocate element-related signals to specific cell types. Distinct patterns of iron accumulation were observed across different cell populations. In the control (Co) SNc, oligodendroglial and astroglial cells hold the highest cellular iron concentration whereas in PD, the iron concentration was increased in most cell types in the substantia nigra except for astroglial cells and ferritin-positive oligodendroglial cells. While iron levels in astroglial cells remain unchanged, ferritin in oligodendroglial cells seems to be depleted by almost half in PD. The highest cellular iron levels in neurons were located in the cytoplasm, which might increase the source of non-chelated Fe3+, implicating a critical increase in the labile iron pool. Indeed, neuromelanin is characterised by a significantly higher loading of iron including most probable the occupancy of low-affinity iron binding sites. Quantitative trace element analysis is essential to characterise iron in oxidative processes in PD. The quantification of iron provides deeper insights into changes of cellular iron levels in PD and may contribute to the research in iron-chelating disease-modifying drugs.

Region-specific distribution of Olig2-expressing astrocytes in adult mouse brain and spinal cord

Olig2 is an important transcription factor essential for the specification and differentiation of oligodendrocytes as well as astrocytes and neurons during developmental stages. However, Olig2 distribution pattern and its relationship among different types of glial cells in the adult central nervous system (CNS) are not well characterized. Here, we systematically examined Olig2 expression pattern in combination with major markers of neurons and glial cells throughout the brain and spinal cord in the adult mice. As expected, Olig2 is universally expressed in oligodendrocytes and oligodendrocyte precursor cells (OPCs), but not in neurons or microglia. Interestingly, we discover a subpopulation of Olig2+ astrocytes that are highly enriched in some specific regions including the olfactory bulb, thalamus, midbrain, medulla, and spinal cord in the adult mice. Moreover, OPCs have high expression level of Olig2, whereas oligodendrocytes and astrocytes have similar level of Olig2 expression. Our results suggest that a distinct population of Olig2+ astrocytes are highly concentrated in discrete regions in the adult CNS. Investigating the functional significance of these Olig2+ astrocytes in both resting state and pathological state of the brain and spinal cord may broaden our understanding on astrocytic heterogeneity and functions.

Graphene glial-interfaces: challenges and perspectives.

Graphene nanosheets are mechanically strong but flexible, electrically conductive and bio-compatible. Thus, due to these unique properties, they are being intensively studied as materials for the next generation of neural interfaces. Most of the literature focused on optimizing the interface between these materials and neurons. However, one of the most common causes of implant failure is the adverse inflammatory reaction of glial cells. These cells are not, as previously considered, just passive and supportive cells, but play a crucial role in the physiology and pathology of the nervous system, and in the interaction with implanted electrodes. Besides providing structural support to neurons, glia are responsible for the modulation of synaptic transmission and control of central and peripheral homeostasis. Accordingly, knowledge on the interaction between glia and biomaterials is essential to develop new implant-based therapies for the treatment of neurological disorders, such as epilepsy, brain tumours, and Alzheimer's and Parkinson's disease. This work provides an overview of the emerging literature on the interaction of graphene-based materials with glial cells, together with a complete description of the different types of glial cells and problems associated with them. We believe that this description will be important for researchers working in materials science and nanotechnology to develop new active materials to interface, measure and stimulate these cells.

One progenitor to generate them all: new evidence for multi-fated neural progenitors.

The past two decades have left behind the old conception of early fate-restricted neural progenitors. The new paradigm is that of a more plastic brain, in which the cellular potential of multi-fated progenitors is progressively restricted. This is observed in the switch from neurogenesis to gliogenesis, but also in the generation of different types of glial cells and neurons at later stages. The mechanisms that establish brain cell diversity or heterogeneity within a single population are starting to be elucidated. The role of cell cycle regulators and dynamics and the asymmetric distribution of cell cargoes during cell division are attracting more attention. Understanding these mechanisms could open the way for new treatments against brain pathologies such as brain tumors or neurodegenerative disorders.

The memory orchestra: the role of astrocytes and oligodendrocytes in parallel to neurons.

For decades, the study of memory has been neuron-centric, yet neurons do not function in isolation. Today we know that neuronal activity is modulated by the environment within which it occurs, and is subject to modulation by different types of glial cells. In this review we summarize recent findings on the functional roles of astrocytes and oligodendrocytes, two major types of glia cells in the adult brain, in memory formation and its cellular underpinnings across multiple time points. We will discuss the different methods that are being used to investigate the astrocytic and oligodendroglial involvement in memory. We shall focus on chemogenetics and optogenetics, which support genetically specificity and high spatiotemporal resolution, attributes that are particularly well suited to the investigation of the contribution of unique cell types at the different stages of memory formation.

Emerging technologies to study glial cells.

Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several technological breakthroughs were achieved, allowing "glio-scientists" to address new challenging biological questions. These technical developments make it possible to study the roles of specific cell types with medium or high-content workflows and perform fine analysis of their mutual interactions in a preserved environment. This review illustrates the potency of several cutting-edge experimental approaches (advanced cell cultures, induced pluripotent stem cell (iPSC)-derived human glial cells, viral vectors, in situ glia imaging, opto- and chemogenetic approaches, and high-content molecular analysis) to unravel the role of glial cells in specific brain functions or diseases. It also illustrates the translation of some techniques to the clinics, to monitor glial cells in patients, through specific brain imaging methods. The advantages, pitfalls, and future developments are discussed for each technique, and selected examples are provided to illustrate how specific "gliobiological" questions can now be tackled.

Sleep Disturbance in Bipolar Disorder: Neuroglia and Circadian Rhythms.

The worldwide prevalence of sleep disorders is approximately 50%, with an even higher occurrence in a psychiatric population. Bipolar disorder (BD) is a severe mental illness characterized by shifts in mood and activity. The BD syndrome also involves heterogeneous symptomatology, including cognitive dysfunctions and impairments of the autonomic nervous system. Sleep abnormalities are frequently associated with BD and are often a good predictor of a mood swing. Preservation of stable sleep–wake cycles is therefore a key to the maintenance of stability in BD, indicating the crucial role of circadian rhythms in this syndrome. The symptom most widespread in BD is insomnia, followed by excessive daytime sleepiness, nightmares, difficulty falling asleep or maintaining sleep, poor sleep quality, sleep talking, sleep walking, and obstructive sleep apnea. Alterations in the structure or duration of sleep are reported in all phases of BD. Understanding the role of neuroglia in BD and in various aspects of sleep is in nascent state. Contributions of the different types of glial cells to BD and sleep abnormalities are discussed in this paper.

The role of astrocytes on the effects of exercise on episodic memory function.

This review discusses the potential role that glial cells may play in influencing the relationship between exercise and episodic memory function. A narrative review methodology is employed. Herein, the different types of glial cells, their implications in subserving episodic memory function, and how exercise can modulate glial cell activity, particularly astrocyte functionality, are discussed. Although additional experimental work is needed, astrocytes appear to play an important role in the exercise-memory interaction. Exercise may increase astrocytic size, attenuate astrogliodegeneration, improve astrocytic aquaporin-4 expression, and increase astrocytic transporter levels. These effects, in turn, may help to increase the number of synapses that neurons form, increase the number of synaptic structures, and increase presynaptic function and postsynaptic receptor localization. Ultimately, these effects may help influence long-term potentiation and episodic memory function.

Expression of glial cells molecules in the optic nerve of adult dromedary camel (Camelus dromedarius): A histological and immunohistochemical analysis.

The optic nerve (ON) is an important organ in the visual system of animals, which transfers electrical impulses towards the brain from the retina. High enrichment of glial cells in ON is known to support neuron and regulate retinal homoeostasis. However, research on immunohistochemical of glial cells proteins in the camel is scanty in available literature. Hence, the current work is an attempt to investigate the histomorphology of camel ON with regard to the expression patterns of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and Iba1 for the three glial subtypes, namely astrocytes, oligodendrocytes and microglia, respectively. Optic nerves from fourteen dromedary camels were dissected and preserved in 10% formalin. Then, the paraffin-embedding sections were subjected for histochemical and immunohistochemical analysis. Our results demonstrated that ON axons aggregate into fascicles that surrounded by light and densely stained glial cells. Then, we examined the myelin sheath using Heidenhain's and Mallory's phosphotungstic acid staining. Immunoassay results revealed that GFAP is enriched in the ON and distributed evenly, whereas MBP and Iba1 were present at scanty levels. Further analysis of mRNA level of GFAP, MBP and Iba1 in the ON confirmed an elevation of GFAP expression compared to MBP and Iba1. We further found partial co-localization of different types of glial cells that reflect their coordinated function in the ON. Although our data provide the first evidence for differential expression pattern of glial proteins, further molecular studies still required to reveal the specific function of these molecules in the camel ON.

Endocannabinoids and Heterogeneity of Glial Cells in Brain Function

Attributable to their strong electrical activity, neurons have long been seen as the main determinants of brain function. Over the last decades, however, this view changed dramatically. A variety of specific roles have been assigned to different types of glial cells. Astrocytes constitute the link between the vascular system and neighboring neurons. They determine ion and transmitter homeostasis, metabolism and neuronal activity. Oligodendrocytes form the myelin sheath. They determine fast signal propagation, timing, and synchronicity. Microglial cells comprise not only the innate immune system of the brain, they also actively regulate synaptogenesis and removal of supra-numerous synapses. In general, microglial cells are quite uniformly distributed across different brain regions.

Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks.

Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (WT; point-to-point communication via private channels, e.g. synaptic transmission) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid). Volume and synaptic transmission become integrated because their chemical signals activate different types of interacting receptors in heteroreceptor complexes located synaptically and extrasynaptically in the plasma membrane. In VT, we focus on the role of the extracellular-vesicle type of VT, and in WT, on the potential role of the tunnelling-nanotube (TNT) type of WT. The so-called exosomes appear to be the major vesicular carrier for intercellular communication but the larger microvesicles also participate. Extracellular vesicles are released from cultured cortical neurons and different types of glial cells and modulate the signalling of the neuronal-glial networks of the CNS. This type of VT has pathological relevance, and epigenetic mechanisms may participate in the modulation of extracellular-vesicle-mediated VT. Gerdes and co-workers proposed the existence of a novel type of WT based on TNTs, which are straight transcellular channels leading to the formation in vitro of syncytial cellular networks found also in neuronal and glial cultures.

Cholesterol in brain disease: sometimes determinant and frequently implicated.

Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell-cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function.

Toward a 3D model of human brain development for studying gene/environment interactions.

This project aims to establish and characterize an in vitro model of the developing human brain for the purpose of testing drugs and chemicals. To accurately assess risk, a model needs to recapitulate the complex interactions between different types of glial cells and neurons in a three-dimensional platform. Moreover, human cells are preferred over cells from rodents to eliminate cross-species differences in sensitivity to chemicals. Previously, we established conditions to culture rat primary cells as three-dimensional aggregates, which will be humanized and evaluated here with induced pluripotent stem cells (iPSCs). The use of iPSCs allows us to address gene/environment interactions as well as the potential of chemicals to interfere with epigenetic mechanisms. Additionally, iPSCs afford us the opportunity to study the effect of chemicals during very early stages of brain development. It is well recognized that assays for testing toxicity in the developing brain must consider differences in sensitivity and susceptibility that arise depending on the time of exposure. This model will reflect critical developmental processes such as proliferation, differentiation, lineage specification, migration, axonal growth, dendritic arborization and synaptogenesis, which will probably display differences in sensitivity to different types of chemicals. Functional endpoints will evaluate the complex cell-to-cell interactions that are affected in neurodevelopment through chemical perturbation, and the efficacy of drug intervention to prevent or reverse phenotypes. The model described is designed to assess developmental neurotoxicity effects on unique processes occurring during human brain development by leveraging human iPSCs from diverse genetic backgrounds, which can be differentiated into different cell types of the central nervous system. Our goal is to demonstrate the feasibility of the personalized model using iPSCs derived from individuals with neurodevelopmental disorders caused by known mutations and chromosomal aberrations. Notably, such a human brain model will be a versatile tool for more complex testing platforms and strategies as well as research into central nervous system physiology and pathology.

Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

BackgroundMesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear.MethodsThe model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins.ResultsWe found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78.ConclusionsThese results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

10Th European Meeting on Glial Cells In Health and Disease

Glial cells are the most abundant cells in the nervous system and have the overall function of ensuring the integrity of neurons and neuronal signaling. There are many different types of glial cells and they are involved in all pathologies of the nervous system. As such, glia are important targets in novel therapeutic strategies.The 10th European Meeting on Glial Cells in Health and Disease is the largest conference of its kind in the world, specialising in the most recent advances in glial cell biology. This meeting brought together the leading international scientists studying the physiology and pathology of glial cells in a 5-day conference, with eight plenary lectures, 32 symposia with 128 lectures from world-renowned experts, poster sessions with over 480 posters summarizing new experimental data, plus workshops and special lectures on state-of-the-art techniques.

Genetic approaches to study glial cells in the rodent brain

The development, function, and pathology of the brain depend on interactions of neurons and different types of glial cells, namely astrocytes, oligodendrocytes, microglia, and ependymal cells. Understanding neuron-glia interactions in vivo requires dedicated experimental approaches to manipulate each cell type independently. In this review, we first summarize techniques that allow for cell-specific gene modification including targeted mutagenesis and viral transduction. In the second part, we describe the genetic models that allow to target the main glial cell types in the central nervous system. The existing arsenal of approaches to study glial cells in vivo and its expansion in the future are key to understand neuron-glia interactions under normal and pathologic conditions.