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| Open AccessOligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice
Whether oligodendrocytes have a role in the development of chronic pain is not clear. Here the authors show that oligodendrocyte depletion causes a neuropathic pain that sets in before demyelination and is independent of immune cell activation and infiltration.
- Simon Gritsch
- , Jianning Lu
- & Rohini Kuner
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Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex
Microglia colonize germinal regions of the developing cerebral cortex and contribute to the regulation of neurogenesis but the mechanisms that regulate this are not clear. Here the authors show that brain progenitor cells, through the secretion of the chemokine Cxcl12, drive microglia to cluster into the germinal regions of the developing mouse cerebral cortex.
- Benedetta Arnò
- , Francesca Grassivaro
- & Luca Muzio
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Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer’s disease mouse model
Astrocytic network alterations are seen in Alzheimer’s disease (AD) but the underlying mechanisms have remained undefined. Here the authors use in vivomulitphoton microscopy to monitor spontaneous network activity of astrocytes in a mouse model of AD, and find that astroglial hyperactivity was largely mediated by activation of the purinergic receptor P2Y1.
- Andrea Delekate
- , Martina Füchtemeier
- & Gabor C. Petzold
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Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent
Specific Schwann cell-axon interactions control the initiation of myelination in the peripheral nervous system. Here the authors show that the tumour suppressor protein Lkb1 is asymmetrically localized to the Schwann cell-axon interface and co-localizes with the polarity protein Par-3 to establish the initiation of myelination.
- Yun-An A. Shen
- , Yan Chen
- & Q. Richard Lu
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The tumour suppressor LKB1 regulates myelination through mitochondrial metabolism
Myelination of peripheral axons by Schwann cells is essential for proper transmission of nerve signals but the underlying mechanisms are not completely understood. Here the authors show that metabolic changes are required to ensure Schwann cell differentiation and proper myelination, and involve the tumour suppressor Lkb1 in regulating this process.
- Shabnam Pooya
- , Xiaona Liu
- & Biplab Dasgupta
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Trans-regulation of oligodendrocyte myelination by neurons through small GTPase Arf6-regulated secretion of fibroblast growth factor-2
The GTPase Arf6, expressed in the central nervous system, is implicated in neural development in vitro, but the roles it plays in vivo are unclear. Akiyama et al. show in vivothat Arf6 positively regulates oligiodendrocyte myelination via the release of the growth factor FGF-2 from hippocampal neurons.
- Masahiro Akiyama
- , Hiroshi Hasegawa
- & Yasunori Kanaho
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Article
| Open AccessMicroglial displacement of inhibitory synapses provides neuroprotection in the adult brain
Microglia play essential roles in sculpting synaptic connections during brain development but their role in the adult brain is less clear. Here the authors show that activated microglia can prophylactically protect the adult rodent brain from injury by migrating to and displacing inhibitory synapses from cortical neurons.
- Zhihong Chen
- , Walid Jalabi
- & Bruce D. Trapp
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| Open AccessRole of astroglia in Down’s syndrome revealed by patient-derived human-induced pluripotent stem cells
Down’s syndrome is characterized by intellectual disability and other neuropathological symptoms. Here, the authors show that astroglia derived from induced pluripotent stem cells from Down’s syndrome patients impair the development of neurons, and that this can be attenuated with the drug minocycline.
- Chen Chen
- , Peng Jiang
- & Wenbin Deng
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Article
| Open AccessAstrocyte response to motor neuron injury promotes structural synaptic plasticity via STAT3-regulated TSP-1 expression
Perineuronal astrocyte reactivity is implicated in functional recovery following nerve injury but exactly how this happens is unclear. Tyzack et al. show that perineuronal astrocytes facilitate the recovery of synaptic inputs to damaged neurons via STAT3-dependent upregulation of the astrocytic protein TSP-1.
- Giulia E. Tyzack
- , Sergey Sitnikov
- & András Lakatos
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Müller cells separate between wavelengths to improve day vision with minimal effect upon night vision
The mammalian retina has an inverted structure, with the photoreceptors buried behind layers of light-scattering cells. Here the authors show through experiment and simulation that specialized Müller cells guide specific wavelengths to the cone photoreceptors while allowing other wavelengths to leak onto the rods.
- Amichai M. Labin
- , Shadi K. Safuri
- & Ido Perlman
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Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia
The removal of dying neurons by microglia plays a key role in both vertebrate nervous system development and several diseases. Here, the authors use a quantitative live imaging approach to investigate neuronal-microglial interactions at single-cell resolution and establish the functions of the phosphatidylserine receptors, TIM-4 and BAI1, in neuronal engulfment.
- Fargol Mazaheri
- , Oksana Breus
- & Francesca Peri
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| Open AccessTranscription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain
In response to neuronal injury or disease, microglia adopt distinct reactive phenotypes via the expression of proteins, such as the purinergic P2X4 receptor. Here, Masuda et al.show that the transcription factor axis, interferon regulatory factor-8 and -5, drives the expression of P2X4 receptor in microglia and the adoption of a reactive phenotype after peripheral nerve injury.
- Takahiro Masuda
- , Shosuke Iwamoto
- & Kazuhide Inoue
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Single-vesicle architecture of synaptobrevin2 in astrocytes
The astrocytic vesicular protein, synaptobrevin2 (Sb2), is implicated in neurotransmitter release, but its vesicular arrangement is poorly understood. Here, Singh et al. use super-resolution fluorescence microscopy to show that the total number of endogenous Sb2 molecules per vesicle is ≤25.
- Priyanka Singh
- , Jernej Jorgačevski
- & Robert Zorec
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Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction
Defects in the cell adhesion molecule GlialCAM, the membrane protein MLC1 and the chloride channel ClC-2 are implicated in leukodystrophy. Here, Hoegg-Beiler et al.show that these proteins form a functional complex to maintain homoeostatic chloride ion transport supporting normal glial function in mice.
- Maja B. Hoegg-Beiler
- , Sònia Sirisi
- & Thomas J. Jentsch
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In vivo conversion of astrocytes to neurons in the injured adult spinal cord
Expression of the transcription factor SOX2 reprogrammes astrocytes into neuroblasts in the adult mouse striatum. Here, the authors use the same approach in the injured adult mouse spinal cord to convert resident astrocytes into neuroblasts that can mature into synapse-forming neurons.
- Zhida Su
- , Wenze Niu
- & Chun-Li Zhang
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| Open AccessLactate-mediated glia-neuronal signalling in the mammalian brain
The astrocytic release of the metabolite L-lactate is implicated in modulating neuronal activity in the brain. Here, the authors show that L-lactate released from astrocytes excites noradrenergic neurons in the locus coeruleus and triggers the release of noradrenaline, increasing network excitability.
- F. Tang
- , S. Lane
- & A. G. Teschemacher
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| Open AccessOptogenetic astrocyte activation modulates response selectivity of visual cortex neurons in vivo
Astrocytes regulate activity within neuronal networks. Here, the authors use photostimulation to activate astrocytes in the mouse visual cortex, and find that this increases excitatory and inhibitory neuronal synaptic transmission via activation of type 1a metabotropic glutamate receptors.
- Gertrudis Perea
- , Aimei Yang
- & Mriganka Sur
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A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes
The physiological function of TWIK-1, a two-pore K+ channel family member, remains unclear. Here, Hwang et al. show that TWIK-1 forms a disulphide-linked heterodimer with TREK-1 to maintain passive conductance and glutamate release in astrocytes.
- Eun Mi Hwang
- , Eunju Kim
- & Jae-Yong Park
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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9
Microglia are specialized immune cells in the brain. Here Åkerblom and colleagues use a microRNA-9-regulated lentiviral vector for the targeted genetic modification of microglia in the rodent brain, presenting a tool that may facilitate functional studies of resident microglia.
- Malin Åkerblom
- , Rohit Sachdeva
- & Johan Jakobsson
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Impaired endolysosomal function disrupts Notch signalling in optic nerve astrocytes
Crystallins are structural proteins that are expressed on the outside of the lens of the eye. Valapala and colleagues find that specific crystallins in retinal astrocytes regulate V-ATPase activity and endolysosomal acidification, to facilitate optimal Notch signalling during retinal development.
- Mallika Valapala
- , Stacey Hose
- & Debasish Sinha
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Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia
Parkinson’s disease is associated with the accumulation of abnormal aggregates of α-synuclein and microglial neuroinflammation. Kim et al. show that α-synuclein oliogomers released by neurons activate microglia by stimulating Toll-like receptor 2 signalling in these cells.
- Changyoun Kim
- , Dong-Hwan Ho
- & Seung-Jae Lee
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| Open AccessSignalling properties of inorganic polyphosphate in the mammalian brain
Inorganic polyphosphates have been identified in the central nervous system. Holmström and colleagues examine neuroglial cultures in vitro and cardiorespiratory responses in vivo, and find that inorganic polyphosphates trigger calcium-dependent activation of astrocytes and increase cardiorespiratory activity.
- Kira M. Holmström
- , Nephtali Marina
- & Andrey Y. Abramov
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| Open AccessFibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation
Multiple sclerosis is characterized by the activation of microglia cells. Davalos et al. investigate the early stages of neuroinflammation in mice and reveal that the plasma protein fibrinogen induces microglial clustering around the brain vasculature, which facilitates lesion formation and focal axonal damage.
- Dimitrios Davalos
- , Jae Kyu Ryu
- & Katerina Akassoglou
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| Open AccessUnfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation
The protein OASIS belongs to the CREB/ATF transcription factor family and is involved in endoplasmic reticulum stress responses. Saito and colleagues show that these stress responses temporally activate OASIS in neural precursor cells, resulting in their differentiation into astrocytes.
- Atsushi Saito
- , Soshi Kanemoto
- & Kazunori Imaizumi
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Direct visualization of microtubules using a genetic tool to analyse radial progenitor-astrocyte continuum in brain
The development of radial progenitor cells and astroglia in the cerebral cortex depends on the microtubule cytoskeleton. Eomet al. have developed a new mouse model where the microtubules of astrocytes and radial glia cells are fluorescently tagged, facilitating the detailed study of microtubule dynamics and development in these cells.
- Tae-Yeon Eom
- , Amelia Stanco
- & E.S. Anton
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| Open AccessGlia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration
The central nervous system contains glial cells, which have been shown to have an important role in neuronal survival. Haradaet al. use transgenic mouse models to show that TrkB, a receptor for the growth factor brain-derived neurotrophic factor, is required for retinal Müller glial cells to provide neuroprotection and regeneration.
- Chikako Harada
- , Xiaoli Guo
- & Takayuki Harada