Contribution Of Glial Cells Research Articles

Neuroinflammation in Post-Traumatic Epilepsy: Pathophysiology and Tractable Therapeutic Targets.

Epilepsy is a common chronic consequence of traumatic brain injury (TBI), contributing to increased morbidity and mortality for survivors. As post-traumatic epilepsy (PTE) is drug-resistant in at least one-third of patients, there is a clear need for novel therapeutic strategies to prevent epilepsy from developing after TBI, or to mitigate its severity. It has long been recognized that seizure activity is associated with a local immune response, characterized by the activation of microglia and astrocytes and the release of a plethora of pro-inflammatory cytokines and chemokines. More recently, increasing evidence also supports a causal role for neuroinflammation in seizure induction and propagation, acting both directly and indirectly on neurons to promote regional hyperexcitability. In this narrative review, we focus on key aspects of the neuroinflammatory response that have been implicated in epilepsy, with a particular focus on PTE. The contributions of glial cells, blood-derived leukocytes, and the blood–brain barrier will be explored, as well as pro- and anti-inflammatory mediators. While the neuroinflammatory response to TBI appears to be largely pro-epileptogenic, further research is needed to clearly demonstrate causal relationships. This research has the potential to unveil new drug targets for PTE, and identify immune-based biomarkers for improved epilepsy prediction.

Contribution of Neurons and Glial Cells to Complement-Mediated Synapse Removal during Development, Aging and in Alzheimer’s Disease

Synapse loss is an early manifestation of pathology in Alzheimer's disease (AD) and is currently the best correlate to cognitive decline. Microglial cells are involved in synapse pruning during development via the complement pathway. Moreover, recent evidence points towards a key role played by glial cells in synapse loss during AD. However, further contribution of glial cells and the role of neurons to synapse pathology in AD remain not well understood. This review is aimed at comprehensively reporting the source and/or cellular localization in the CNS—in microglia, astrocytes, or neurons—of the triggering components (C1q, C3) of the classical complement pathway involved in synapse pruning in development, adulthood, and AD.

Hippocampal Astrocytes in Migrating and Wintering Semipalmated Sandpiper Calidris pusilla.

Seasonal migratory birds return to the same breeding and wintering grounds year after year, and migratory long-distance shorebirds are good examples of this. These tasks require learning and long-term spatial memory abilities that are integrated into a navigational system for repeatedly locating breeding, wintering, and stopover sites. Previous investigations focused on the neurobiological basis of hippocampal plasticity and numerical estimates of hippocampal neurogenesis in birds but only a few studies investigated potential contributions of glial cells to hippocampal-dependent tasks related to migration. Here we hypothesized that the astrocytes of migrating and wintering birds may exhibit significant morphological and numerical differences connected to the long-distance flight. We used as a model the semipalmated sandpiper Calidris pusilla, that migrates from northern Canada and Alaska to South America. Before the transatlantic non-stop long-distance component of their flight, the birds make a stopover at the Bay of Fundy in Canada. To test our hypothesis, we estimated total numbers and compared the three-dimensional (3-D) morphological features of adult C. pusilla astrocytes captured in the Bay of Fundy (n = 249 cells) with those from birds captured in the coastal region of Bragança, Brazil, during the wintering period (n = 250 cells). Optical fractionator was used to estimate the number of astrocytes and for 3-D reconstructions we used hierarchical cluster analysis. Both morphological phenotypes showed reduced morphological complexity after the long-distance non-stop flight, but the reduction in complexity was much greater in Type I than in Type II astrocytes. Coherently, we also found a significant reduction in the total number of astrocytes after the transatlantic flight. Taken together these findings suggest that the long-distance non-stop flight altered significantly the astrocytes population and that morphologically distinct astrocytes may play different physiological roles during migration.

Heterogeneity and function of hippocampal macroglia.

The contribution of glial cells to normal and impaired hippocampal function is increasingly being recognized, although important questions as to the mechanisms that these cells use for their crosstalk with neurons and capillaries are still unanswered or lead to controversy. Astrocytes in the hippocampus are morphologically variable and a single cell contacts with its processes more than 100,000 synapses. They predominantly express inward rectifier K+ channels and transporters serving homeostatic function but may also release gliotransmitters to modify neuronal signaling and brain circulation. Intracellular Ca2+ transients are key events in the interaction of astrocytes with neurons and the vasculature. Hippocampal NG2 glia represent a population of cells with proliferative capacity throughout adulthood. Intriguingly, they receive direct synaptic input from pyramidal neurons and interneurons and express a multitude of ion channels and receptors. Despite in-depth knowledge about the features of these transmembrane proteins, the physiological impact of NG2 glial cells and their synaptic input remain nebulous. Because of the low abundance of oligodendrocytes in the hippocampus, limited information is available about their specific properties. Given the multitude of signaling molecules expressed by the various types of hippocampal glial cells (and because of space constraints), we focus, in this review, on those properties that are considered key for the interaction of the respective cell type with its neighborhood.

Updates on immunity and inflammation in Parkinson disease pathology.

Studies in the last decade have suggested the association of both neuroinflammatory processes and immune responses in Parkinson disease (PD) pathology. PD pathology is related to depleted dopamine levels, α-synuclein aggregation, and death of nigrostriatal dopaminergic neurons. Reports have suggested central and peripheral inflammation in the prodromal stage of the disease, which is sustained during disease progression. Alongside the activation of peripheral immune system exacerbates the dissonant central inflammatory responses and could contribute in synergistic neurodegeneration. Activated glial cells contribute significantly in the neuroinflammatory process during the occurrence of the disease and are also acknowledged as a hallmark of disease progression. However, the contribution of glial cells is not well defined in the context of neurodegeneration and neuroprotection. This review provides an overview of the roles of immune and inflammatory responses and their consequences in PD disease pathogenesis and also discusses possible therapeutic strategies for PD based on these findings.

Activation of PKC triggers rescue of NPC1 patient specific iPSC derived glial cells from gliosis

BackgroundNiemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. The pathological mechanisms, underlying NPC1 are not yet completely understood. Especially the contribution of glial cells and gliosis to the progression of NPC1, are controversially discussed. As an analysis of affected cells is unfeasible in NPC1-patients, we recently developed an in vitro model system, based on cells derived from NPC1-patient specific iPSCs. Here, we asked if this model system recapitulates gliosis, observed in non-human model systems and NPC1 patient post mortem biopsies. We determined the amount of reactive astrocytes and the regulation of the intermediate filaments GFAP and vimentin, all indicating gliosis. Furthermore, we were interested in the assembly and phosphorylation of these intermediate filaments and finally the impact of the activation of protein kinase C (PKC), which is described to ameliorate the pathogenic phenotype of NPC1-deficient fibroblasts, including hypo-phosphorylation of vimentin and cholesterol accumulation.MethodsWe analysed glial cells derived from NPC1 patient specific induced pluripotent stem cells, carrying different NPC1 mutations. The amount of reactive astrocytes was determined by means of immuncytochemical stainings and FACS-analysis. Semi-quantitative western blot was used to determine the amount of phosphorylated GFAP and vimentin. Cholesterol accumulation was analysed by Filipin staining and quantified by Amplex Red Assay. U18666A was used to induce NPC1 phenotype in unaffected cells of the control cell line. Phorbol 12-myristate 13-acetate (PMA) was used to activate PKC.ResultsImmunocytochemical detection of GFAP, vimentin and Ki67 revealed that NPC1 mutant glial cells undergo gliosis. We found hypo-phosphorylation of the intermediate filaments GFAP and vimentin and alterations in the assembly of these intermediate filaments in NPC1 mutant cells. The application of U18666A induced not only NPC1 phenotypical accumulation of cholesterol, but characteristics of gliosis in glial cells derived from unaffected control cells. The application of phorbol 12-myristate 13-acetate, an activator of protein kinase C resulted in a significantly reduced number of reactive astrocytes and further characteristics of gliosis in NPC1-deficient cells. Furthermore, it triggered a restoration of cholesterol amounts to level of control cells.ConclusionOur data demonstrate that glial cells derived from NPC1-patient specific iPSCs undergo gliosis. The application of U18666A induced comparable characteristics in un-affected control cells, suggesting that gliosis is triggered by hampered function of NPC1 protein. The activation of protein kinase C induced an amelioration of gliosis, as well as a reduction of cholesterol amount. These results provide further support for the line of evidence that gliosis might not be only a secondary reaction to the loss of neurons, but might be a direct consequence of a reduced PKC activity due to the phenotypical cholesterol accumulation observed in NPC1. In addition, our data support the involvement of PKCs in NPC1 disease pathogenesis and suggest that PKCs may be targeted in future efforts to develop therapeutics for NPC1 disease.

Ethyl pyruvate does not require microglia for mediating neuroprotection after excitotoxic injury.

Ethyl pyruvate (EP) mediates protective effects after neuronal injury. Besides a direct conservation of damaged neurons, the modulation of indigenous glial cells has been suggested as one important mechanism for EP-related neuroprotection. However, the specific contribution of glial cells is still unknown. Organotypic hippocampal slice cultures (OHSC) were excitotoxically lesioned by 50μmol/L N-methyl-D-aspartate (NMDA, for 4hours) or left untreated. In an additional OHSC subset, microglia was depleted using the bisphosphonate clodronate (100μg/mL) before lesion. After removal of NMDA, EP containing culture medium (0.84μmol/L, 8.4μmol/L, 42μmol/L, 84μmol/L, 168μmol/L) was added and incubated for 72hours. OHSC were stained with propidium iodide to visualize degenerating neurons and isolectin IB4 -FITC to identify microglia. Effects of EP at concentrations of 0.84, 8.4, and 84μmol/L (0-48hours) were analyzed in the astrocytic scratch wound assay. EP significantly reduced neurodegeneration following induced excitotoxicity except for 168μmol/L. For 84μmol/L, a reduction in the microglia cells was observed. Microglia depletion did not affect neuronal survival after EP treatment. EP decelerated astrocytic wound closure at 48hours after injury. EP-mediated neuroprotection seems to be mediated by astrocytes and/or neurons.

18F]FDG PET signal is driven by astroglial glutamate transport.

Contributions of glial cells to neuroenergetics have been the focus of extensive debate. Here we provide the first positron emission tomography (PET) evidence that activation of the astrocytic glutamate transport via GLT-1 triggers widespread but graded glucose uptake in the rodent brain. Our results highlight the need for a reevaluation of the interpretation of [18F]FDG PET data, whereby astrocytes would be recognized to contribute significantly to the [18F]FDG signal.

Glial Cell Contributions to Auditory Brainstem Development.

Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits.

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn−/−;SMN2tg/0;SMN1SC). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms.

Glia as drivers of abnormal neuronal activity.

Reactive astrocytes have been proposed to become incompetent bystanders in epilepsy as a result of cellular changes rendering them unable to perform important housekeeping functions. Indeed, successful surgical treatment of mesiotemporal lobe epilepsy hinges on the removal of the glial scar. New research now extends the role of astrocytes, suggesting that they may drive the disease process by impairing the inhibitory action of neuronal GABA receptors. Here we discuss studies that include hyperexcitability resulting from impaired supply of astrocytic glutamine for neuronal GABA synthesis, and epilepsy resulting from genetically induced astrogliosis or malignant transformation, both of which render the inhibitory neurotransmitter GABA excitatory. In these examples, glial cells alter the expression or function of neuronal proteins involved in excitability. Although epilepsy has traditionally been thought of as a disease caused by changes in neuronal properties exclusively, these new findings challenge us to consider the contribution of glial cells as drivers of epileptogenesis in acquired epilepsies.

Early and persistent abnormal decoding by glial cells at the neuromuscular junction in an ALS model.

Amyotrophic lateral sclerosis (ALS) is a late-onset neuromuscular disease characterized by progressive loss of motor neurons (MNs) preceded by neuromuscular junction (NMJ) denervation. Despite the importance of NMJ denervation in ALS, the mechanisms involved remain unexplored and ill defined. The contribution of glial cells in the disease has been highlighted, including axonal Schwann cell activation that precedes the decline of motor function and the onset of hindlimb paralysis. Because NMJ denervation occurs early in the process and that perisynaptic Schwann cells (PSCs), glial cells at the NMJ, regulate morphological stability, integrity, and repair of the NMJ, one could predict that PSC functions would be altered even before denervation, contributing to NMJ malfunctions. We tested this possibility using a slowly progressive model of ALS (SOD1(G37R) mice). We observed a normal NMJ organization at a presymptomatic stage of ALS (120 d), but PSC detection of endogenous synaptic activity revealed by intracellular Ca(2+) changes was enhanced compared with their wild-type littermates. This inappropriate PSC decoding ability was associated with an increased level of neurotransmitter release and dependent on intrinsic glial properties related to enhanced muscarinic receptor activation. The alteration of PSC muscarinic receptor functions also persists during the preonset stage of the disease and became dependent on MN vulnerability with age. Together, these results suggest that PSC properties are altered in the disease process in a manner that would be detrimental for NMJ repair. The impairments of PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.

Neurodegeneration and neuroinflammation: two processes, one target.

The etiology of neurodegenerative diseases is diverse, however most of them share common characteristics: accumulation of misfolded proteins, chronic and sustained neuroinflammation, and the dysfunction and death of certain populations of neurons. The brain of Alzheimer's disease (AD) patients presents amyloid plaques and aggregation of hyperphosphorylated tau. The latter is also present in neurodegenerative tauopathies and in Parkinson's disease (PD). Aggregates of α-synuclein is the characteristic hallmark of PD. In amyotrophic lateral sclerosis (ALS) the mutation of SOD1 promotes its accumulation; and the polyglutamine expansion in huntingtin protein favors its aggregation in Huntington's disease (HD). Thus, the initial proteinopathy could be responsible for triggering the activation of the immunological defenses in the nervous system, as it has been demonstrated in some cases. Microglia and astrocytes are the main glial cells involved in the innate inflammatory response in the central nervous system (CNS). These cells are capable of detecting danger signals, and when activated they secrete inflammatory mediators to try to protect or prevent damage. However, in some cases the inflammatory response becomes sustained by an amplified feedback of release of factors between microglia and astrocytes that further activate these cells. This promotes the recruitment of more glial cells that prolongs and up-regulates the neuroinflammatory response contributing to the progression of the disease (the review of Glass et al. (2010) outlines in detail the contribution of glial cells in neurodegenerative diseases). Neurodegeneration has a remarkable apoptotic component; sustained neuroinflammatory response along with the deregulation of protective mechanisms trigger neuronal death.

Microglia centered pathogenesis in ALS: insights in cell interconnectivity.

Amyotrophic lateral sclerosis (ALS) is the most common and most aggressive form of adult motor neuron (MN) degeneration. The cause of the disease is still unknown, but some protein mutations have been linked to the pathological process. Loss of upper and lower MNs results in progressive muscle paralysis and ultimately death due to respiratory failure. Although initially thought to derive from the selective loss of MNs, the pathogenic concept of non-cell-autonomous disease has come to the forefront for the contribution of glial cells in ALS, in particular microglia. Recent studies suggest that microglia may have a protective effect on MN in an early stage. Conversely, activated microglia contribute and enhance MN death by secreting neurotoxic factors, and impaired microglial function at the end-stage may instead accelerate disease progression. However, the nature of microglial–neuronal interactions that lead to MN degeneration remains elusive. We review the contribution of the neurodegenerative network in ALS pathology, with a special focus on each glial cell type from data obtained in the transgenic SOD1G93A rodents, the most widely used model. We further discuss the diverse roles of neuroinflammation and microglia phenotypes in the modulation of ALS pathology. We provide information on the processes associated with dysfunctional cell–cell communication and summarize findings on pathological cross-talk between neurons and astroglia, and neurons and microglia, as well as on the spread of pathogenic factors. We also highlight the relevance of neurovascular disruption and exosome trafficking to ALS pathology. The harmful and beneficial influences of NG2 cells, oligodendrocytes and Schwann cells will be discussed as well. Insights into the complex intercellular perturbations underlying ALS, including target identification, will enhance our efforts to develop effective therapeutic approaches for preventing or reversing symptomatic progression of this devastating disease.

Nav1.9 expression in magnocellular neurosecretory cells of supraoptic nucleus

Osmoregulation in mammals is tightly controlled by the release of vasopressin and oxytocin from magnocellular neurosecretory cells (MSC) of the supraoptic nucleus (SON). The release of vasopressin and oxytocin in the neurohypophysis by axons of MSC is regulated by bursting activity of these neurons, which is influenced by multiple sources, including intrinsic membrane properties, paracrine contributions of glial cells, and extrinsic synaptic inputs. Previous work has shown that bursting activity of MSC is tetrodotoxin (TTX)-sensitive, and that TTX-S sodium channels Nav1.2, Nav1.6 and Nav1.7 are expressed by MSC and upregulated in response to osmotic challenge in rats. The TTX-resistant sodium channels, NaV1.8 and Nav1.9, are preferentially expressed, at relatively high levels, in peripheral neurons, where their properties are linked to repetitive firing and subthreshold electrogenesis, respectively, and are often referred to as “peripheral” sodium channels. Both sodium channels have been implicated in pain pathways, and are under study as potential therapeutic targets for pain medications which might be expected to have minimal CNS side effects. We show here, however, that Nav1.9 is expressed by vasopressin- and oxytocin-producing MSC of the rat supraoptic nucleus (SON). We also show that cultured MSC exhibit sodium currents that have characteristics of Nav1.9 channels. In contrast, Nav1.8 is not detectable in the SON. These results suggest that Nav1.9 may contribute to the firing pattern of MSC of the SON, and that careful assessment of hypothalamic function be performed as NaV1.9 blocking agents are studied as potential pain therapies.

Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co‐culture model of inflammation

The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms of action of several antiepileptic drugs (AEDs) have been proposed. However, their direct effects on glial cells have been rarely investigated. We aimed to investigate the effect of commonly used AEDs on glial viability, the gap junctional network, the microglial activation, and cytokine expression in an in vitro astroglia/microglia co-culture model. Primary astrocytic cultures were prepared from brains of postnatal (P0-P2) Wistar rats and co-cultured with a physiologic amount of 5%, as well as 30% microglia in order to mimic inflammatory conditions. Co-cultures were treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHE), and gabapentin (GBT). Viability and proliferation were measured using the tetrazolium (MTT) assay. The microglial activation state was determined by immunocytochemical labeling. The astroglial connexin 43 (Cx43) expression was measured by Western blot analysis. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) cytokine levels were measured by the quantitative sandwich enzyme immunosorbent assay (ELISA). Astrocytes, co-cultured with 5% microglia (M5 co-cultures), showed a dose-dependent, significant reduction in glial viability after incubation with PHE and CBZ. Furthermore, VPA led to highly significant microglial activation at all doses examined. The antiinflammatory cytokine TGF-β1 release was induced by high doses of GBT and PHE. Astrocytes co-cultured with 30% microglia (M30 co-cultures) revealed a dose-dependent significant reduction in glial viability after incubation with PHE, accompanied by increased TGF-β1 and TNF-α levels. However, CBZ significantly reduced the amount of activated microglial cells and increased the total number of inactivated microglia. Finally, CBZ resulted in reduced viability at all doses examined. CNS inflammation is characterized by a disturbance of glial cell functions. Strong microglial activation, a typical hallmark of inflammation, was induced by VPA in M5 and continued in M30 co-cultures. With regard to the direct relation between CNS inflammation and seizures, VPA seems to be unsuitable for reducing inflammatory conditions. The reverse effect was achieved after CBZ. We noticed significant microglial inactivation, after incubation of the M30 co-cultures. In conclusion, we suggest that AEDs with antiinflammatory glial features are beneficial for seizures caused by persistent brain inflammation.

Mechanism of suppression of sustained neuronal spiking under high-frequency stimulation

Using Hodgkin–Huxley and isolated subthalamic nucleus (STN) model neurons as examples, we show that electrical high-frequency stimulation (HFS) suppresses sustained neuronal spiking. The mechanism of suppression is explained on the basis of averaged equations derived from the original neuron equations in the limit of high frequencies. We show that for frequencies considerably greater than the reciprocal of the neuron’s characteristic time scale, the result of action of HFS is defined by the ratio between the amplitude and the frequency of the stimulating signal. The effect of suppression emerges due to a stabilization of the neuron’s resting state or due to a stabilization of a low-amplitude subthreshold oscillation of its membrane potential. Intriguingly, although we neglect synaptic dynamics, neural circuity as well as contribution of glial cells, the results obtained with the isolated high-frequency stimulated STN model neuron resemble the clinically observed relations between stimulation amplitude and stimulation frequency required to suppress Parkinsonian tremor.

Purinergic modulation of norepinephrine release and uptake in rat brain cortex: contribution of glial cells

The pathogenesis of psychiatric and neurodegenerative diseases is often associated with a deregulation of noradrenergic transmission. Considering the potential involvement of purinergic signaling in the modulation of noradrenergic transmission in the brain cortex, this study aimed to identify the P2Y receptor subtypes involved in the modulation of neuronal release and neuronal/glial uptake of norepinephrine. Electrical stimulation (100 pulses at 5 Hz) of rat cortical slices induced norepinephrine release that was inhibited by ATP and ADP (0.01-1 mM), adenosine 5'-O-(2-thiodiphosphate) (ADPβS, 0.03-0.3 mM), and UDP (0.1-1 mM). The effect of ADPβS was mediated by P2Y1 receptors and possibly by A1/P2Y1 heterodimers since it was attenuated by the A1 receptor antagonist DPCPX and by the P2Y1 receptor antagonist MRS 2500 but was resistant to the effect of adenosine deaminase (ADA). UDP inhibited norepinephrine release through activation of P2Y6 receptors, an effect that was abolished by the P2Y6 receptor antagonist MRS 2578 and by DPCPX, indicating that it depends on the formation and/or release of adenosine and activation of A1 receptors. Supporting this hypothesis, the inhibitory effect of UDP was also prevented by inhibition of ectonucleotidases, by ADA and was attenuated by the inhibitor of nucleoside transporter 6-[(4-nitrobenzyl)thio]-9-β-d-ribofuranosylpurine (NBTI). Additionally, the inhibitory effect of UDP was attenuated when norepinephrine uptake 1 or 2 was inhibited. In astroglial cultures, ADPβS and UDP increased norepinephrine uptake mainly by activation of P2Y1 and P2Y6 receptors, respectively. The results indicate that neuronal and glial P2Y1 and P2Y6 receptors may represent new targets of intervention to regulate noradrenergic transmission in CNS diseases.

Oligodendroglia: new players in amyotrophic lateral sclerosis

The contribution of glial cells to the neuropathology and phenotype of amyotrophic lateral sclerosis (ALS) has become a focus for basic and translational research. Whereas astrocytes and microglia are studied in great detail, the contribution of oligodendrocytes has been relatively neglected. Oligodendrocytes, one of the most important glial cells of ectodermal origin, serve to endow axons with myelin sheaths that are important for the propagation of signals in the CNS. Very recently, it has been demonstrated that they also contribute to axonal energy supply and metabolism (Lee et al. , 2012). Oligodendrocytes have been shown to contribute to the neuropathology of ALS (Neumann et al. , 2007; Seilhean et al. , 2009; MacKenzie et al. , 2011). In some subforms of the disease, such as that seen in SOD1D90A mutation carriers, there is evidence that the pyramidal tracts are demyelinated, but research on their functional contribution to the disease process is in its early stages. Now, in work that is complementary …

Commentary 2 (The Contribution of Glial Cells and Water Channel Aquaporin-4 in the Neuropathology of Cardiac Arrest is Still Ignored)

The contribution of glial cells and water channel aquaporin-4 in the neuropathology of cardiac arrest is still ignored