Glial biology | Nature

Article
17 April 2024 | Open Access

Network-level encoding of local neurotransmitters in cortical astrocytes

A study investigates subcellular, single-cell and network-level comunication within the astrocyte network in response to the two major neurotransmitter inputs.

Michelle K. Cahill
, Max Collard
& Kira E. Poskanzer

Article
13 March 2024 | Open Access

Mitochondrial complex I activity in microglia sustains neuroinflammation

Blocking mitochondrial complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in vivo in an animal disease model.

L. Peruzzotti-Jametti
, C. M. Willis
& S. Pluchino

Article
13 March 2024 | Open Access

APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia

A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.

Michael S. Haney
, Róbert Pálovics
& Tony Wyss-Coray

Article
28 February 2024 | Open Access

Crym-positive striatal astrocytes gate perseverative behaviour

In mice, a population of astrocytes in the central striatum, characterized by expression of μ-crystallin, has a role in perseveration phenotypes that are often associated with human neuropsychiatric disorders.

Matthias Ollivier
, Joselyn S. Soto
& Baljit S. Khakh

Article | 12 December 2023

A molecular switch for neuroprotective astrocyte reactivity

The authors identify a molecular switch that regulates the balance between neurotoxic and neuroprotective astrocyte populations, with potential application in the treatment of glaucoma and other optic neuropathies.

Evan G. Cameron
, Michael Nahmou
& Jeffrey L. Goldberg

Article
06 September 2023 | Open Access

Specialized astrocytes mediate glutamatergic gliotransmission in the CNS

A subpopulation of astrocytes selectively expresses synaptic-like glutamate-release machinery, actively secretes the transmitter and is localized to discrete sites in the hippocampus.

Roberta de Ceglia
, Ada Ledonne
& Andrea Volterra

Article
31 May 2023 | Open Access

Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease

Mouse models show that myelin dysfunction and associated inflammation increase with age, which can promote amyloid-β deposition and therefore risk of developing Alzheimer’s disease.

Constanze Depp
, Ting Sun
& Klaus-Armin Nave

Article | 26 April 2023

Inhibitory input directs astrocyte morphogenesis through glial GABA_BR

Inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis.

Yi-Ting Cheng
, Estefania Luna-Figueroa
& Benjamin Deneen

Article
12 April 2023 | Open Access

Astrocyte–neuron subproteomes and obsessive–compulsive disorder mechanisms

Analyses of the proteomes of astrocytes and neurons in a cell-specific and subcompartment-specific manner reveal distinct roles for these cell types that are relevant to obsessive–compulsive disorder and perhaps other brain disorders.

Joselyn S. Soto
, Yasaman Jami-Alahmadi
& Baljit S. Khakh

Article
14 December 2022 | Open Access

Microglia regulate central nervous system myelin growth and integrity

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Niamh B. McNamara
, David A. D. Munro
& Veronique E. Miron

Article | 16 November 2022

APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

APOE4 is associated with widespread gene expression changes across all cell types of the human brain, altered cholesterol homeostasis and transport signalling pathways, and decreased myelination in the brain.

Joel W. Blanchard
, Leyla Anne Akay
& Li-Huei Tsai

Article | 28 September 2022

Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry

Aberrantly formed microglia due to an adverse prenatal environment affect long-term microglia reactivity and proper striatal circuit development in mice

Lindsay N. Hayes
, Kyongman An
& Akira Sawa

Article | 31 August 2022

Hippocampal astrocytes encode reward location

Astrocytes can encode an expected reward location in familiar spatial contexts.

Adi Doron
, Alon Rubin
& Inbal Goshen

Article | 10 August 2022

Pyramidal neuron subtype diversity governs microglia states in the neocortex

Spatial and single-cell transcriptomic characterization of microglia in the mouse somatosensory cortex show that the state of these cells is determined by signals from diverse surrounding neurons.

Jeffrey A. Stogsdill
, Kwanho Kim
& Paola Arlotta

Article | 25 May 2022

Divergent transcriptional regulation of astrocyte reactivity across disorders

Transcriptional changes associated with astrocyte reactivity are highly heterogeneous and are customized from vast numbers of potential DEGs through context-specific combinatorial interactions amongst transcriptional regulators.

Joshua E. Burda
, Timothy M. O’Shea
& Michael V. Sofroniew

Article | 20 October 2021

Regulation of intestinal immunity and tissue repair by enteric glia

Enteric glial cells have tissue-wide immunoregulatory roles through the upregulation of IFNγ-dependent genes both at steady state and after parasite infection, promoting immune homeostasis and CXCL10-mediated tissue repair after pathogen-induced intestinal damage in mice.

Fränze Progatzky
, Michael Shapiro
& Vassilis Pachnis

Article | 06 October 2021

Neurotoxic reactive astrocytes induce cell death via saturated lipids

Astrocytes can respond to diseases and injuries of the central nervous system by driving the death of neurons and mature oligodendrocytes through the delivery of long-chain saturated fatty acids contained in lipoparticles.

Kevin A. Guttenplan
, Maya K. Weigel
& Ben A. Barres

Article | 14 July 2021

Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease

Interleukin-3 signalling from astrocytes to microglia readies microglia to defend against Alzheimer’s disease.

Cameron S. McAlpine
, Joseph Park
& Filip K. Swirski

Article | 23 December 2020

Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis

In adult mice, astrocytes carry out phagocytosis of excitatory hippocampal synapses through MEGF10 to maintain synaptic and circuit homeostasis.

Joon-Hyuk Lee
, Ji-young Kim
& Won-Suk Chung

Article | 11 November 2020

Chemico-genetic discovery of astrocytic control of inhibition in vivo

A cell-surface fragment complementation strategy is used to identify the proteome at the junction of astrocytes and synapses in vivo, and shows that NRCAM expressed in astrocytes has a key role in regulating inhibitory synapse function.

Tetsuya Takano
, John T. Wallace
& Scott H. Soderling

Article | 07 October 2020

Microglia-organized scar-free spinal cord repair in neonatal mice

In neonatal mice, scar-free healing after spinal cord injury is organized by microglia, and transplantation of neonatal microglia or peptidase-inhibitor-treated adult microglia into adult mice after injury improves healing and axon regrowth.

Yi Li
, Xuelian He
& Zhigang He

Article | 30 September 2020

Negative feedback control of neuronal activity by microglia

Microglia, the brain’s immune cells, suppress neuronal activity in response to synaptic ATP release and alter behavioural responses in mice.

Ana Badimon
, Hayley J. Strasburger
& Anne Schaefer

Article | 31 August 2020

Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency

In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

Jiasheng Zhang
, Dmitry Velmeshev
& Eric J. Huang

Article | 18 September 2019

Electrical and synaptic integration of glioma into neural circuits

Neurons form synapses onto glioma cells, and depolarization of glioma membranes promotes glioma growth in vivo, whereas blocking electrochemical signalling blocks tumour growth.

Humsa S. Venkatesh
, Wade Morishita
& Michelle Monje

Letter | 15 August 2019

Niche stiffness underlies the ageing of central nervous system progenitor cells

Aged progenitor cells in the rat central nervous system can be made to behave as young cells by reducing the stiffness of the tissue microenvironment, or by inhibiting the mechanosensitive protein PIEZO1.

Michael Segel
, Björn Neumann
& Kevin J. Chalut

Letter | 23 January 2019

Altered human oligodendrocyte heterogeneity in multiple sclerosis

Single-nucleus RNA sequencing analysis identifies different subclusters of oligodendroglia in white matter from individuals with multiple sclerosis compared with controls, and these differences may be important for understanding disease progression.

Sarah Jäkel
, Eneritz Agirre
& Gonçalo Castelo-Branco

Letter | 23 January 2019

Dynamics of oligodendrocyte generation in multiple sclerosis

There are no new oligodendrocytes in potentially remyelinated multiple sclerosis shadow plaques, although oligodendrocyte generation is increased in the normal appearing white matter of patients with aggressive disease, informing the development of new therapies.

Maggie S. Y. Yeung
, Mehdi Djelloul
& Jonas Frisén

Article | 15 February 2018

Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression

Increased expression of the potassium channel Kir4.1 on astrocytes in the lateral habenula drives neuronal bursting in rodent models of depression.

Yihui Cui
, Yan Yang
& Hailan Hu

Article | 09 November 2017

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis

Astrocyte morphogenesis depends on interactions between astrocytic neuroligins and neuronal neurexins.

Jeff A. Stogsdill
, Juan Ramirez
& Cagla Eroglu

Letter | 14 June 2017

Microglia-dependent synapse loss in type I interferon-mediated lupus

Abnormal behavioural phenotypes and synapse loss in the brain of lupus-prone mice are prevented by blocking type I interferon signalling, which is further shown to stimulate microglial phagocytosis of neuronal material in the brains of these mice.

Allison R. Bialas
, Jessy Presumey
& Michael C. Carroll

Article | 18 January 2017

Neurotoxic reactive astrocytes are induced by activated microglia

A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.

Shane A. Liddelow
, Kevin A. Guttenplan
& Ben A. Barres

Letter | 09 November 2016

Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour

Calcium signalling in astrocytes, driven through the octopamine/tyramine receptor and the TRP channel Water witch, is essential for neuromodulation and sensory responses in Drosophila larvae.

Zhiguo Ma
, Tobias Stork
& Marc R. Freeman

Letter | 13 July 2016

Glial-cell-derived neuroregulators control type 3 innate lymphoid cells and gut defence

Neurotrophic factors produced by enteric glia in response to microbiota and alarmin cues regulate IL-22 production by group 3 innate lymphoid cells in the gut; disruption of this pathway leads to impaired clearance of Citrobacter rodentium and defects in epithelial integrity in a model of intestinal inflammation.

Sales Ibiza
, Bethania García-Cassani
& Henrique Veiga-Fernandes

Letter | 06 April 2016

TAM receptors regulate multiple features of microglial physiology

Microglial phagocytosis is required for neurogenic niche maintenance and response to injury; the TAM kinases Mer and Axl are expressed by microglia in the adult CNS, and mediate the clearance of apoptotic cells from the niche.

Lawrence Fourgeaud
, Paqui G. Través
& Greg Lemke

Letter | 13 January 2016

Proton-gated Ca²⁺-permeable TRP channels damage myelin in conditions mimicking ischaemia

Ischaemia damages nerve myelin by depriving neurons and their myelinating oligodendrocytes of oxygen and glucose; here it is shown that ischaemic damage is caused through the H⁺-dependent activation of TRPA1 channels, and not via glutamate receptors of the NMDA type, as previously thought, providing a new mechanism and promising therapeutic targets for diseases as diverse and prevalent as cerebral palsy, spinal cord injury, stroke and multiple sclerosis.

Nicola B. Hamilton
, Karolina Kolodziejczyk
& David Attwell

Letter | 25 December 2013

Intranasal epidermal growth factor treatment rescues neonatal brain injury

Diffuse white matter injury is common in very preterm infants; here, enhanced epidermal growth factor receptor signalling in oligodendrocyte precursor cells in a mouse model of such injury is shown to increase cellular and functional recovery.

Joseph Scafidi
, Timothy R. Hammond
& Vittorio Gallo

Article | 24 November 2013

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

This study describes comprehensive synaptic engulfment by astrocytes, mediating synapse elimination in an activity-dependent manner; this elimination process involves the MEGF10 and MERTK phagocytic pathways and persists into adulthood, with mutant mice that lack these pathways in astrocytes exhibiting a failure to refine retinogeniculate connections during development.

Won-Suk Chung
, Laura E. Clarke
& Ben A. Barres

Research Highlights | 19 September 2012

Social isolation thins neural sheath

Research Highlights | 22 August 2012

Flushing proteins from the brain

Article | 11 July 2012

Oligodendroglia metabolically support axons and contribute to neurodegeneration

Disruption of the lactate transporter monocarboxylate transporter 1 (MCT1), which is highly enriched within oligodendroglia and reduced in patients with amyotrophic lateral sclerosis (ALS), causes axon damage and neurodegeneration in animal and cell culture models, suggesting a fundamental role for MCT1 in metabolic support of axons and ALS pathogenesis.

Youngjin Lee
, Brett M. Morrison
& Jeffrey D. Rothstein

News Feature | 30 May 2012

Microglia: The constant gardeners

Once thought to be passive sentinels, microglia now seem to be crucial for pruning back neurons during development.

Virginia Hughes

Letter | 27 May 2012

Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors

Glypican 4 and glypican 6 are identified as astrocyte-secreted signals that induce the formation of functional, rather than structural, synapses through the recruitment to the neuron surface of the GluA1 subunits of the AMPA glutamate receptor.

Nicola J. Allen
, Mariko L. Bennett
& Ben A. Barres

Letter | 29 April 2012

Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

After myelination, oligodendrocytes are able to survive without mitochondrial respiration, suggesting that they can switch to aerobic glycolysis and release lactate.

Ursula Fünfschilling
, Lotti M. Supplie
& Klaus-Armin Nave

News | 18 April 2012

Nanomaterials offer hope for cerebral palsy

Rabbits with brain injuries hop again after treatment with dendrimers.

Amy Maxmen

Letter | 28 March 2012

Local generation of glia is a major astrocyte source in postnatal cortex

A major source of glia in the postnatal cortex in mice is the local proliferation of differentiated astrocytes.

Woo-Ping Ge
, Atsushi Miyawaki
& Lily Yeh Jan

Letter | 18 March 2012

Wild-type microglia arrest pathology in a mouse model of Rett syndrome

Transplanting bone marrow from wild-type mice into MECP2-lacking mice results in wild-type microglial engraftment, extends lifespan and reduces symptoms of disease such as breathing and locomotor abnormalities, implicating microglia in the pathophysiology of Rett syndrome.