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| Open AccessMicroglia-neuron interaction at nodes of Ranvier depends on neuronal activity through potassium release and contributes to remyelination
Microglia are important for brain homeostasis and plasticity. The mechanisms underlying microglia-neuron interactions are still unclear. Here, the authors show that microglia preferentially interact with the nodes of Ranvier along axons. This interaction is modulated by neuronal activity and contributes to remyelination in mice.
- R. Ronzano
- , T. Roux
- & A. Desmazières
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Article
| Open AccessOligodendrocytic Na+-K+-Cl– co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain
Brain plasticity declines with age. Here, the authors show that NKCC1 regulates oligodendrocyte activity, facilitating neuronal plasticity during juvenile. Inducing activation of oligodendrocytic NKCC1 results in restoration of neuronal plasticity in the adult mouse brain.
- Yoshihiko Yamazaki
- , Yoshifumi Abe
- & Kenji F. Tanaka
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Article
| Open AccessTen-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain
Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.
- Ming Zhang
- , Jian Wang
- & Xianghui Zhao
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Article
| Open AccessCortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination
Myelination patterns of different neurons in grey matter have not been fully defined. Here, the authors show that axon diameter and neuronal identity influence myelination patterns in the intact mouse somatosensory cortex. In vivo imaging revealed that remyelination altered myelin patterns but restored overall myelin content on distinct neuron subtypes.
- Cody L. Call
- & Dwight E. Bergles
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Article
| Open AccessMicroglia modulate stable wakefulness via the thalamic reticular nucleus in mice
Here, the authors show that microglia depletion results in unstable wakefulness and altered levels of ceramide, influencing microglia in the mouse thalamic reticular nucleus (TRN). Stable wakefulness can be restored by activation of the TRN or inhibition of ceramide production in the mouse brain.
- Hanxiao Liu
- , Xinxing Wang
- & Qiaojie Xiong
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Article
| Open AccessConservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
Astrocytes are important players in brain development, homeostasis, and disease. Here, the authors compare the transcriptional profiles of human and mouse astrocytes. They report species-specific susceptibility to oxidative stress and response to hypoxic and inflammatory conditions.
- Jiwen Li
- , Lin Pan
- & Ye Zhang
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Article
| Open AccessPhospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer’s disease
Microglia can clear amyloid plaques in Alzheimer’s disease. Here, the authors show that specific isoforms of the phospholipid forming APOE lipoproteins activate microglia in pre-clinical mouse models of Alzheimer’s disease.
- Nicholas F. Fitz
- , Kyong Nyon Nam
- & Radosveta Koldamova
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Article
| Open AccessTET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelin repair in adult mice, but is defective with aging.
- Sarah Moyon
- , Rebecca Frawley
- & Patrizia Casaccia
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Article
| Open AccessProhibitin 1 is essential to preserve mitochondria and myelin integrity in Schwann cells
Prohibitin 2 can localize to the axon-Schwann-cell interface and is required for myelin formation. Here, the authors show that deletion of prohibitin 1 in Schwann cells instead triggers severe myelin loss likely caused by mitochondrial dysfunction, and not rescued by inhibition of the ensuing integrated stress response.
- Gustavo Della-Flora Nunes
- , Emma R. Wilson
- & M. Laura Feltri
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Article
| Open AccessImpaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice
Astrocytes contribute to autism spectrum disorder (ASD) pathophysiology. Here, the authors show that IP3R2 conditional KO mice show ASD-like behaviours and identify astrocyte-derived ATP as a modulator of these behaviours in mice.
- Qian Wang
- , Ying Kong
- & Tian-Ming Gao
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Article
| Open AccessTranscriptional signature in microglia associated with Aβ plaque phagocytosis
Microglia associated with Aβ plaques may have a distinct transcriptional signature compared to those in plaque-free areas of the brain in Alzheimer’s disease (AD) models. Here the authors show that amyloid plaque phagocytosis is associated with a specific microglia transcriptional signature in a mouse model of AD.
- Alexandra Grubman
- , Xin Yi Choo
- & Jose M. Polo
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Article
| Open AccessBrain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling
Lipophorin receptors (LpRs) regulate structural and functional development of neurons in Drosophila. Here authors demonstrate how short isoforms of LpR1 mediates astrocyte lipid shuttling to neuron through interacting with glia lipoprotein GLaz and the role of this pathway in dendritic morphogenesis in the fly brain.
- Jun Yin
- , Emma Spillman
- & Quan Yuan
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Article
| Open AccessMicroglial neuropilin-1 promotes oligodendrocyte expansion during development and remyelination by trans-activating platelet-derived growth factor receptor
Oligodendrocyte precursor cell (OPC) proliferation and differentiation is greater in white matter than gray matter. Here, the authors show regulation of OPC proliferation in white matter involved trans-activation of PDGFRα on OPCs via Nrp1 expressed by adjacent microglia.
- Amin Sherafat
- , Friederike Pfeiffer
- & Akiko Nishiyama
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Article
| Open AccessLoss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration
Microglial SIRPα regulates synaptic pruning during development. Its role in neurodegeneration is unclear. Here, the authors show microglial SIRPα declines in the model of Alzheimer’s disease, leading to excessive microglia mediated synapse elimination as well as impaired cognitive function.
- Xin Ding
- , Jin Wang
- & Liang Li
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Article
| Open AccessOvercoming the inhibitory microenvironment surrounding oligodendrocyte progenitor cells following experimental demyelination
Demyelination results in impairments in oligodendrocyte progenitor cell recruitment. Here the authors identify sulfatase 1/2 as a potential modulator of myelination by modulating the microenvironment around oligodendrocyte progenitor cells.
- Darpan Saraswat
- , Hani J. Shayya
- & Fraser J. Sim
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Article
| Open AccessAxonal chemokine-like Orion induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling
Astrocytes can engulf axonal debris in the developing brain. However, the mechanisms regulating astrocyte recruitment to the proper axons is unclear. Here, the authors identify Orion as a signal for astrocyte infiltration and engulfment to the mushroom bodies in the Drosophila developing brain.
- Ana Boulanger
- , Camille Thinat
- & Jean-Maurice Dura
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Article
| Open AccessSchwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8
Schwann cells (SCs) can acquire a repair phenotype following nerve injury. Here, the authors show that stromal SCs in ganglioneuromas express nerve-repair genes. Importantly, neuroblastoma cells respond to repair-related SCs increasing neuronal differentiation and reducing proliferation via EGFL8.
- Tamara Weiss
- , Sabine Taschner-Mandl
- & Inge M. Ambros
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Article
| Open AccessLoss of Quaking RNA binding protein disrupts the expression of genes associated with astrocyte maturation in mouse brain
Quaking RNA binding protein (QKI) is known for its role in oligodendrocyte maturation. Here, the authors define the QKI targets in the mouse brain and show that loss of QKI disrupts the expression of cell maturation-associated genes in astrocytes in vivo.
- Kristina Sakers
- , Yating Liu
- & Joseph D. Dougherty
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| Open AccessSingle-cell transcriptomic reveals molecular diversity and developmental heterogeneity of human stem cell-derived oligodendrocyte lineage cells
Brain myelinating oligodendrocytes are rare and difficult to isolate, which has limited data on their development. Here the authors develop a reporter for scalable purification of human pluripotent stem cell derived oligodendrocyte lineage cells, and use this to map differentiation using single cell RNA-sequencing,
- Xitiz Chamling
- , Alyssa Kallman
- & Donald J. Zack
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Article
| Open AccessFilamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex
The mechanisms underlying the transmission of Tau in astrocytes are unclear. Here, the authors show that the entry of filamentous recombinant human Tau into astrocytes via the integrin αV/ β1 complex stimulates integrin signaling, resulting in activation of NFκB and astrocyte conversion towards a neurotoxic state.
- Peng Wang
- & Yihong Ye
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Article
| Open AccessAstrocyte deletion of α2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway
Mutations of α2-Na/K ATPase can cause familial hemiplegic migraine via unclear mechanisms. Here, the authors show that deletion of α2-Na/K ATPase in astrocytes results in gene expression and metabolic changes leading to cortical spreading depression and episodic transient motor paralysis in mice.
- Sarah E. Smith
- , Xiaoying Chen
- & Azad Bonni
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Article
| Open AccessEthanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release
The effects of norepinephrine on sensory processing in cortical networks are altered by recreational drugs like ethanol. The authors show that ethanol suppresses the activation of astrocytes by inhibiting norepinephrine release which may contribute to the cognitive effects of alcohol intoxication.
- Liang Ye
- , Murat Orynbayev
- & Martin Paukert
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Article
| Open AccessSingle cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease
Imbalance of microglial phenotypes in the aging brain might underlie their involvement in late onset neurodegenerative diseases. Here we report the population structure of microglia in the aged human brain and the reduction of a particular microglia subset in individuals with Alzheimer’s disease .
- Marta Olah
- , Vilas Menon
- & Philip L. De Jager
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Article
| Open AccessAstrocytic pyruvate dehydrogenase kinase-2 is involved in hypothalamic inflammation in mouse models of diabetes
Hypothalamic inflammation is involved in the pathogenesis of diabetes. The underlying mechanisms are unclear. Here, the authors show that astrocytic PDK2 ablation or inhibition attenuates hypothalamic inflammation in mouse models of diabetes.
- Md Habibur Rahman
- , Anup Bhusal
- & Kyoungho Suk
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Article
| Open AccessDistinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury
The oligodendrocyte lineage is known for its transcriptional heterogeneity, but the functional consequences of this are unclear. Here, the authors show that distinct populations of mature oligodendrocytes have spatial preferences in the brain and spinal cord and show different responses to spinal cord injury.
- Elisa M. Floriddia
- , Tânia Lourenço
- & Gonçalo Castelo-Branco
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| Open AccessA role of oligodendrocytes in information processing
Oligodendrocytes myelinate and metabolically support axons. The role of myelination in information processing beyond regulation of conduction velocity is unclear. Here, the authors show that myelination contributes to sustained stimulus perception in the auditory cortex, shaping neuronal responses.
- Sharlen Moore
- , Martin Meschkat
- & Klaus-Armin Nave
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Article
| Open AccessGene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer’s disease
Mutations in TREM2 alter risk for Alzheimer’s disease, though the mechanisms underlying risk in human cells are unclear. Here, the authors use iPS-microglia and chimeric mice to highlight altered survival, phagocytosis, migration, and transcriptional programs in microglia lacking TREM2.
- Amanda McQuade
- , You Jung Kang
- & Mathew Blurton-Jones
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Article
| Open AccessMyelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits
Myelination optimizes conduction speed of excitatory neurons. However, whether myelination of interneurons (INs) refines cortical networks is unclear. Here, the authors show that INs myelination shapes feedforward inhibition of mouse cortical sensory circuits and impacts whisker-mediated behaviour.
- Najate Benamer
- , Marie Vidal
- & María Cecilia Angulo
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Article
| Open AccessAstrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle
Several mechanisms contribute to the maintenance of constant extracellular pH, essential for normal brain function. Here the authors show that astrocytes help to control local brain pH via a neuronal activity-dependent release of bicarbonate by the electrogenic sodium bicarbonate cotransporter 1.
- Shefeeq M. Theparambil
- , Patrick S. Hosford
- & Alexander V. Gourine
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| Open AccessSchwann-cell-derived CMTM6 restricts radial axonal growth
Myelinating Schwann cells control the diameter of the axons they ensheath by an unknown mechanism. In a recent article in Nature Communications, Eichel and colleagues identify the tetraspan protein CMTM6 as a regulator of axonal caliber.
- Nimrod Elazar
- & Elior Peles
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Article
| Open AccessD-serine mitigates cell loss associated with temporal lobe epilepsy
Temporal lobe epilepsy (TLE) can be unresponsive to treatment. Here, the authors show that treatment with D-Serine mitigates TLE and acts on neurons and glia, attenuating neuronal loss and reducing astro- and microgliosis in rodents.
- Stephen Beesley
- , Thomas Sullenberger
- & Sanjay S. Kumar
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Article
| Open AccessGABA uptake transporters support dopamine release in dorsal striatum with maladaptive downregulation in a parkinsonism model
GABA transporters expressed in the striatum may affect behaviour. Here the authors investigate the contribution of GABA transporters on astrocytes to the regulation of dopamine release in the striatum, and show decreased expression of GAT-1 and GAT-3 in a mouse model of Parkinsonism.
- Bradley M. Roberts
- , Natalie M. Doig
- & Stephanie J. Cragg
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Article
| Open AccessMyelin replacement triggered by single-cell demyelination in mouse cortex
Myelination is a highly regulated phenomenon. Here, the authors show that demyelination induced by the loss of a single oligodendrocyte triggers replenishment of a specific fraction the original myelin and myelination of previously unmyelinated axons in the mouse cortex.
- Nicolas Snaidero
- , Martina Schifferer
- & Thomas Misgeld
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Article
| Open AccessSatellite glial cells promote regenerative growth in sensory neurons
The contribution of satellite glia to peripheral nerve regeneration is unclear. Here, the authors show that satellite glia are transcriptionally distinct from Schwann cells, share similarities with astrocytes, and, upon injury, they contribute to axon regeneration via Fasn-PPARα signalling pathway.
- Oshri Avraham
- , Pan-Yue Deng
- & Valeria Cavalli
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Article
| Open AccessThe atypical chemokine receptor 3 interacts with Connexin 43 inhibiting astrocytic gap junctional intercellular communication
The atypical chemokine receptor 3 (ACKR3) is known to regulate cell migration, but the underlying mechanisms are unclear. Here, the authors show, from an interactome analysis, ACKR3 association with the gap junction protein Connexin 43 in vivo and ACKR3-mediated inhibition of astrocyte gap junctional communication.
- Amos Fumagalli
- , Joyce Heuninck
- & Philippe Marin
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Article
| Open AccessCMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves
Myelinating cells differentially myelinate axons of different diameters, however whether they can also restrict radial axonal growth remained unclear. Here, the authors show that CMTM6 in Schwann cells restricts axon diameters, affecting sensory nerve conduction and behavioral performance.
- Maria A. Eichel
- , Vasiliki-Ilya Gargareta
- & Hauke B. Werner
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Article
| Open AccessWrapping glia regulates neuronal signaling speed and precision in the peripheral nervous system of Drosophila
Conduction velocity and precise neuronal transmission depend on axonal diameter and ephatic coupling, respectively. Here, the authors showed that wrapping glia regulates both conduction speed and precision of neuronal signalling in the Drosophila peripheral nervous system.
- Rita Kottmeier
- , Jonas Bittern
- & Christian Klämbt
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Article
| Open AccessCircadian control of brain glymphatic and lymphatic fluid flow
Glymphatic function is increased during the rest phase while more cerebrospinal fluid (CSF) drains directly to the lymphatic system during the active phase. The water channel aquaporin-4 supports these endogenous, circadian rhythms in CSF distribution.
- Lauren M. Hablitz
- , Virginia Plá
- & Maiken Nedergaard
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Article
| Open AccessCTCF-mediated chromatin looping in EGR2 regulation and SUZ12 recruitment critical for peripheral myelination and repair
Myelination by Schwann cells (SC) in the peripheral nervous system is essential for motor function, and dysregulation of SC myelination can lead to various neuropathies. Here the authors describe a critical role of CCCTC-binding factor (CTCF)-dependent chromatin reorganization in peripheral myelination and myelin regeneration after injury.
- Jincheng Wang
- , Jiajia Wang
- & Q. Richard Lu
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Article
| Open AccessKnockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
Astrocyte activation may contribute to neurodegenerative disease. Here the authors show that the combined knockout of three factors known to promote astrogliosis, IL-1α, TNFα and C1qa, leads to improved survival in the SOD1G93A mouse model of ALS.
- Kevin A. Guttenplan
- , Maya K. Weigel
- & Ben A. Barres
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Article
| Open AccessAstrocytes modulate sensory-evoked neuronal network activity
Astrocytes respond to neurotransmitters with calcium transients stimulating the release of gliotransmitters that regulate synaptic and neuronal functions. Here, the authors show that cortical astrocytes also respond to sensory inputs and regulate sensory-evoked neuronal network activity.
- Justin Lines
- , Eduardo D. Martin
- & Alfonso Araque
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Article
| Open AccessSynucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling
The nanoscale organisation of the brain extracellular space can be studied in vivo. Here, the authors investigate how it changes in response to α-synuclein pathology, and identify interactions between microglia and the extracellular matrix.
- Federico N. Soria
- , Chiara Paviolo
- & Erwan Bezard
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Article
| Open AccessEEF1A1 deacetylation enables transcriptional activation of remyelination
The molecular mechanisms regulating remyelination are unclear. Here, the authors show that promoting deacetylation of eEF1A1 prevents the translocation of Sox10 outside the nucleus, contributing to maintaining the expression of Sox10 target genes and increasing remyelination efficiency.
- Mert Duman
- , Adrien Vaquié
- & Claire Jacob
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Article
| Open AccessAstrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep
Despite evidence that astrocytes mediate sleep-dependent function, the involved signaling mechanisms are unknown. The authors show that astrocytic Ca2+ signalling exhibits distinct features across the sleep-wake cycle and ablation of this Ca2+ signalling pathway impairs slow wave sleep.
- Laura Bojarskaite
- , Daniel M. Bjørnstad
- & Erlend A. Nagelhus
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Article
| Open AccessThe TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Here, the authors show that microglia-specific deletion of TSPO and chemical inhibition of TSPO prevent neuroinflammation and vascular damage in a mouse model of AMD.
- Anne Wolf
- , Marc Herb
- & Thomas Langmann
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Article
| Open AccessPTSD is associated with neuroimmune suppression: evidence from PET imaging and postmortem transcriptomic studies
Neuroinflammation has been proposed to accompany the peripheral inflammation observed in PTSD. Here, authors find lower in vivo and postmortem levels of neuroimmune marker TSPO (translocator protein) in PTSD, in association with greater PTSD severity and higher plasma CRP.
- Shivani Bhatt
- , Ansel T. Hillmer
- & Kelly P. Cosgrove
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Article
| Open AccessInterneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia
Dysfunction of GABAergic neurons in the prefrontal cortex has been reported in schizophrenia. Here, the authors use the apomorphine-susceptible rat, which displays some schizophrenia-like behaviors, and show that interneurons in the medial prefrontal cortex are hypomyelinated, which may contribute to this behavioral phenotype.
- Dorien A. Maas
- , Vivian D. Eijsink
- & Gerard J. M. Martens
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Article
| Open AccessEndothelin-1 signaling maintains glial progenitor proliferation in the postnatal subventricular zone
Endothelin-1 (ET-1) is a vasoconstrictor molecule that is also present in the developing and injured CNS. Here the authors show that ET-1 is present in the postnatal subventricular zone and acts to regulate maintenance and proliferation of radial glial cells and oligodendrocyte progenitor cells.
- Katrina L. Adams
- , Giulia Riparini
- & Vittorio Gallo
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Article
| Open AccessLipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury
The regeneration dynamics following peripheral nerve injury differs among species. Here, the authors compared transcriptomic and lipid metabolism changes in murine and human Schwann cells in vivo and ex vivo sural nerves, underlying their switch from myelinating to repair state following injury.
- Sofia Meyer zu Reckendorf
- , Christine Brand
- & Bernd Knöll