This comprehensive advanced text on the biology and pathology of glial cells--the most numerous cells in the brain and an emerging field in neuroscience--offers detailed coverage of the morphology ...and interrelationships between glial cells and neurones in different parts of the nervous system. An accompanying website offers downloadable figures and slides.
The importance of glial cells has become increasingly apparent over the past 20 years, yet compared to neurons we still know relatively little about these essential cells. Most critical glial cell ...functions are conserved in Drosophila glia, often using the same key molecular players as their vertebrate counterparts. The relative simplicity of the Drosophila nervous system, combined with a vast array of powerful genetic tools, allows us to further dissect the molecular composition and functional roles of glia in ways that would be much more cumbersome or not possible in higher vertebrate systems. Importantly, Drosophila genetics allow for in vivo manipulation, and their transparent body wall enables in vivo imaging of glia in intact animals throughout early development. Here we discuss recent advances in Drosophila glial development detailing how these cells take on their mature morphologies and interact with neurons to perform their important functional roles in the nervous system.
Neuroglia Kettenmann, Helmut; Ransom, Bruce R
2012, 2012-11-29
eBook
Neuroglia, the third edition, is the long-awaited revision of the most highly regarded reference volume on glial cells. This indispensable edition has been completely revised, greatly enlarged, and ...enhanced with four-color figures throughout, all in response to the tremendous amount of new information that has accumulated since the previous edition seven years ago.
Retinal regeneration is robust in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms that suppress the reprogramming of Müller ...glia into neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this interaction are unknown. We used the chick model in vivo to investigate Nuclear Factor kappa B (NF-κB) signaling, a critical regulator of inflammation, during the reprogramming of Müller glia into proliferating progenitors. We find that components of the NF-κB pathway are dynamically regulated by Müller glia after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses the formation of proliferating MGPCs. Following microglia ablation, the effects of NF-κB-agonists on MGPC-formation are reversed, suggesting that signals provided by reactive microglia influence how NF-κB impacts Müller glia reprogramming. We propose that NF-κB is an important signaling "hub" that suppresses the reprogramming of Müller glia into proliferating MGPCs and this "hub" coordinates signals provided by reactive microglia.
An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used ...Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secretion pathway involving extracellular vesicles. Disrupting the release of extracellular vesicles or the expression of ferritin heavy chain in oligodendrocytes causes neuronal loss and oxidative damage in mice. Our data point to a role of oligodendrocytes in providing an antioxidant defense system to support neurons against iron-mediated cytotoxicity.
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•A screen in Drosophila identifies glial molecules with vital functions for neurons•Depletion of glial ferritin heavy chain results in iron-mediated axonal damage•Ferritin heavy chain is secreted by oligodendrocytes in mice•Disrupting its release or expression results in neuronal damage in aged mice
Mukherjee et al. found that glia provide an antioxidant defense system to support neurons against iron-mediated cytotoxicity in Drosophila. In mice, ferritin heavy chain is secreted by oligodendrocytes, employing extracellular vesicles. Disrupting the release or the expression of ferritin heavy chain in oligodendrocytes causes neuronal damage in aged mice.
How cells tightly control the formation and turnover of branched actin filament arrays to drive cell motility, endocytosis, and other cellular processes is still not well understood. Here, we ...investigated the mechanistic relationship between two binding partners of the Arp2/3 complex, glia maturation factor (GMF) and cortactin. Individually, GMF and cortactin have opposite effects on the stability of actin filament branches, but it is unknown how they work in concert with each other to govern branch turnover. Using TIRF microscopy, we observe that GMF’s branch destabilizing activities are potently blocked by cortactin (IC50 = 1.3 nM) and that this inhibition requires direct interactions of cortactin with Arp2/3 complex. The simplest model that would explain these results is competition for binding Arp2/3 complex. However, we find that cortactin and GMF do not compete for free Arp2/3 complex in solution. Further, we use single molecule analysis to show that cortactin’s on-rate (3 ×107 s−1 M−1) and off-rate (0.03 s−1) at branch junctions are minimally affected by excess GMF. Together, these results show that cortactin binds with high affinity to branch junctions, where it blocks the destabilizing effects of GMF, possibly by a mechanism that is allosteric in nature. In addition, the affinities we measure for cortactin at actin filament branch junctions (Kd = 0.9 nM) and filament sides (Kd = 206 nM) are approximately 20-fold stronger than previously reported. These observations contribute to an emerging view of molecular complexity in how Arp2/3 complex is regulated through the integration of multiple inputs.
•Cortactin blocks GMF destabilization of actin filament branch junctions.•Direct interactions of cortactin with Arp2/3 are required to block GMF effects.•Excess GMF does not interfere with cortactin binding to Arp2/3 or branch junctions.
•Purified Hemozoid is internalized into human primary cells.•Internalization triggers toxicity in neurons and astrocytes.•Hemozoid does not need additional host and parasite factors to be toxic.
...Malaria, caused by an intracellular protozoan parasite of the genus Plasmodium, is one of the most important infectious diseases worldwide. In 2017, a total of 219 millions cases were reported with 435,000 deaths related to malaria. A major complication of malaria infection is cerebral malaria (CM), characterized by enhanced blood-brain barrier permeability, leukocyte infiltration and/or activation, and neuronal dropout resulting in coma and death in significant numbers of individuals, especially children. Despite the high incidence and mortality, the pathogenesis of cerebral malaria is not well characterized. Hemozoin (HMZ) or “malaria pigment,” a by-product of intraerythrocytic parasite-mediated hemoglobin catabolism, is released into the bloodstream after lysis of the host infected erythrocyte. The effects of HMZ on brain cells has not been studied due to the contamination/adhesion/aggregation of the HMZ with host and toxic parasitic factors. We now demonstrate that extracellular purified HMZ is taken up by human neurons and astrocytes, resulting in cellular dysfunction and toxicity. These findings contribute to a better understanding of the neuropathogenesis of CM and provide evidence that HMZ accumulation in the bloodstream could result in CNS compromise. Thus, alternative approaches to reducing circulating HMZ could serve as a potential treatment.
The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse neurons are closely associated with glial cells ...originating from the neural crest. However, the molecular nature and diversity among peripheral glia are not understood. Here, we used single-cell RNA sequencing to profile developing and mature glia from somatosensory dorsal root ganglia and auditory spiral ganglia. We found that glial precursors (GPs) in these two systems differ in their transcriptional profiles. Despite their unique features, somatosensory and auditory GPs undergo convergent differentiation to generate molecularly uniform myelinating and non-myelinating Schwann cells. By contrast, somatosensory and auditory satellite glial cells retain system-specific features. Lastly, we identified a glial signature gene set, providing new insights into commonalities among glia across the nervous system. This survey of gene expression in peripheral glia constitutes a resource for understanding functions of glia across different sensory modalities.
•DRG and cochlea glial precursors differ in their transcriptome and prevalence•Convergent differentiation in DRG and cochlea produces Schwann cells•DRG and cochlea satellite glia differ in their transcriptomes•Identification of a glial gene set common to PNS glia, supporting cells and CNS glia
Tasdemir-Yilmaz et al. present an scRNA-seq dataset of developing and mature peripheral glia from the somatosensory and auditory systems. They provide insights into development of peripheral glia types and how the glial transcriptome varies along with needs of the sensory system and present a common glial gene set among multiple glial subtypes.
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