Enhanced oligodendrocyte maturation and myelination in a mouse model of Timothy syndrome.

Abstract:

:To study the role of L-type voltage-gated Ca++ channels in oligodendrocyte development, we used a mouse model of Timothy syndrome (TS) in which a gain-of-function mutation in the α1 subunit of the L-type Ca++ channel Cav1.2 gives rise to an autism spectrum disorder (ASD). Oligodendrocyte progenitor cells (OPCs) isolated from the cortex of TS mice showed greater L-type Ca++ influx and displayed characteristics suggestive of advanced maturation compared to control OPCs, including a more complex morphology and higher levels of myelin protein expression. Consistent with this, expression of Cav1.2 channels bearing the TS mutation in wild-type OPCs triggered process formation and promoted oligodendrocyte-neuron interaction via the activation of Ca++ /calmodulin-dependent protein kinase II. To ascertain whether accelerated OPC maturation correlated with functional enhancements, we examined myelination in the TS brain at different postnatal time points. The expression of myelin proteins was significantly higher in the corpus callosum, cortex and striatum of TS animals, and immunohistochemical analysis for oligodendrocyte stage-specific markers revealed an increase in the density of myelinating oligodendrocytes in several areas of the TS brain. Along the same line, electron microscopy studies in the corpus callosum of TS animals showed significant increases both in the percentage of myelinated axons and in the thickness of myelin sheaths. In summary, these data indicate that OPC development and oligodendrocyte myelination is enhanced in the brain of TS mice, and suggest that this mouse model of a syndromic ASD is a useful tool to explore the role of L-type Ca++ channels in myelination.

journal_name

Glia

journal_title

Glia

authors

Cheli VT,Santiago González DA,Zamora NN,Lama TN,Spreuer V,Rasmusson RL,Bett GC,Panagiotakos G,Paez PM

doi

10.1002/glia.23468

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

2324-2339

issue

11

eissn

0894-1491

issn

1098-1136

journal_volume

66

pub_type

杂志文章

相关文献

GLIA文献大全
  • Bcl-2-expressing oligodendrocytes in multiple sclerosis lesions.

    abstract::Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system leading to selective destruction of myelin sheaths and/or oligodendrocytes. The immunological mechanisms responsible for myelin destruction and the primary target of the immune response have not yet been identified. Prior studies h...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Kuhlmann T,Lucchinetti C,Zettl UK,Bitsch A,Lassmann H,Brück W

    更新日期:1999-10-01 00:00:00

  • Anti-ACSA-2 defines a novel monoclonal antibody for prospective isolation of living neonatal and adult astrocytes.

    abstract::Astrocytes are the most abundant cell type of the central nervous system and cover a broad range of functionalities. We report here the generation of a novel monoclonal antibody, anti-astrocyte cell surface antigen-2 (Anti-ACSA-2). Flow cytometry, immunohistochemistry and immunocytochemistry revealed that Anti-ACSA-2 ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23140

    authors: Kantzer CG,Boutin C,Herzig ID,Wittwer C,Reiß S,Tiveron MC,Drewes J,Rockel TD,Ohlig S,Ninkovic J,Cremer H,Pennartz S,Jungblut M,Bosio A

    更新日期:2017-06-01 00:00:00

  • Tripchlorolide protects neuronal cells from microglia-mediated beta-amyloid neurotoxicity through inhibiting NF-kappaB and JNK signaling.

    abstract::Recent research has focused on soluble oligomeric assemblies of beta-amyloid peptides (Abeta) as the proximate cause of neuroinflammation, synaptic loss, and the eventual dementia associated with Alzheimer's disease (AD). In this study, tripchlorolide (T4), an extract of Tripterygium wilfordii Hook. F (TWHF), was stud...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20844

    authors: Pan XD,Chen XC,Zhu YG,Chen LM,Zhang J,Huang TW,Ye QY,Huang HP

    更新日期:2009-08-15 00:00:00

  • Differentiation of induced pluripotent stem cells into functional oligodendrocytes.

    abstract::The technology to generate autologous pluripotent stem cells (iPS cells) from almost any somatic cell type has brought various cell replacement therapies within clinical research. Besides the challenge to optimize iPS protocols to appropriate safety and GMP levels, procedures need to be developed to differentiate iPS ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21159

    authors: Czepiel M,Balasubramaniyan V,Schaafsma W,Stancic M,Mikkers H,Huisman C,Boddeke E,Copray S

    更新日期:2011-06-01 00:00:00

  • Foxp3 is a novel repressor of microglia activation.

    abstract::Forkhead transcription factor 3 (Foxp3) is critical for generating CD4(+)CD25(+) regulatory T cells. However, its role in microglia has not been identified. Here, we show that Foxp3 is expressed in microglia and is upregulated upon activation. In Foxp3 mutant mice (Foxp3(sf)), microglia release higher levels of inflam...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.21006

    authors: Chung HS,Lee JH,Kim H,Lee HJ,Kim SH,Kwon HK,Im SH,Bae H

    更新日期:2010-08-01 00:00:00

  • Pure astrocyte cultures derived from cells isolated from mature brain.

    abstract::Enriched preparations of oligodendrocytes, isolated either from adult bovine brain or from 30-day-old rat brain, eventually yield cultures in MEM-15% calf serum that contain, in addition to oligodendrocytes, proliferating astrocytes and variable numbers of fibroblast-like cells. If these cultures are switched to a ser...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440010608

    authors: Norton WT,Farooq M,Chiu FC,Bottenstein JE

    更新日期:1988-01-01 00:00:00

  • Homotypic cell contact-dependent inhibition of astrocyte proliferation.

    abstract::The normal adult vertebrate nervous system is a relative quiescent tissue in terms of cell proliferation. However, astrocytes in many regions of the central nervous system (CNS) retain the capacity to undergo cell division. To examine the mechanisms that regulate the proliferation of astrocytes in the CNS we have util...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199804)22:4<379::aid-glia7

    authors: Nakatsuji Y,Miller RH

    更新日期:1998-04-01 00:00:00

  • Differential regulation of microglial keratan sulfate immunoreactivity by proinflammatory cytokines and colony-stimulating factors.

    abstract::Resident microglia of the rat CNS express a unique type of keratan sulfate immunoreactivity (KS-IR) that is lacking on peripheral monocytes/macrophages and associated with a so far unknown proteoglycan core protein. Microglial KS-IR is downregulated during T-cell-mediated autoimmune inflammation but largely preserved ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(200006)30:4<401::aid-glia9

    authors: Jander S,Schroeter M,Fischer J,Stoll G

    更新日期:2000-06-01 00:00:00

  • Cell death in the oligodendrocyte lineage: a molecular perspective of life/death decisions in development and disease.

    abstract::Cell death in the oligodendrocyte lineage occurs during development and in pathological conditions as the result of a balance between opposing molecular signals. This review focuses on the molecular mechanisms of activation of signal transduction pathways affecting life/death decisions in progenitor cells and in matur...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1098-1136(20000115)29:2<124::aid-gli

    authors: Casaccia-Bonnefil P

    更新日期:2000-01-15 00:00:00

  • Pathophysiology of glia in perinatal white matter injury.

    abstract::Injury to the preterm brain has a particular predilection for cerebral white matter. White matter injury (WMI) is the most common cause of brain injury in preterm infants and a major cause of chronic neurological morbidity including cerebral palsy. Factors that predispose to WMI include cerebral oxygenation disturbanc...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.22658

    authors: Back SA,Rosenberg PA

    更新日期:2014-11-01 00:00:00

  • Stress-induced structural and functional modifications of astrocytes-Further implicating glia in the central response to stress.

    abstract::An organism's response to stress requires activation of multiple brain regions. This can have long-lasting effects on synaptic transmission and plasticity that likely provide adaptive benefits. Recent evidence implicates not only neurones, but also glial cells in the regulation of the central response to stress. Inten...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.23610

    authors: Murphy-Royal C,Gordon GR,Bains JS

    更新日期:2019-10-01 00:00:00

  • The nutritive function of glia is regulated by signals released by neurons.

    abstract::The idea of a metabolic coupling between neurons and astrocytes in the brain has been entertained for about 100 years. The use recently of simple and well-compartmentalized nervous systems, such as the honeybee retina or purified preparations of neurons and glia, provided strong support for a nutritive function of gli...

    journal_title:Glia

    pub_type: 杂志文章

    doi:

    authors: Tsacopoulos M,Poitry-Yamate CL,Poitry S,Perrottet P,Veuthey AL

    更新日期:1997-09-01 00:00:00

  • FGFs stimulate IGF binding protein synthesis without affecting IGF synthesis in rat astroblasts in primary culture.

    abstract::The production of insulin-like growth factor (IGF)-I and -II and their binding proteins (BPs) has been studied in new-born rat astroblasts at confluency in primary culture. Under the influence of fibroblast growth factors (FGFs) (acidic and basic), the morphology of the astroblasts was altered, 125I-deoxyuridine incor...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440040405

    authors: Loret C,Janet T,Labourdette G,Schneid H,Binoux M

    更新日期:1991-01-01 00:00:00

  • Transport of L-arginine in cultured glial cells.

    abstract::Uptake of radiolabelled L-arginine was studied in four different kinds of glial cultures, in astroglia-rich primary cultures derived from neonatal rat and mouse brains, in pure murine astrocyte cultures, and in rat glioma cells C6-BU-1. A saturable component of uptake was found in all cases with KM values between 15 a...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440110307

    authors: Schmidlin A,Wiesinger H

    更新日期:1994-07-01 00:00:00

  • Isolated growth cones stimulate proliferation of cultured Schwann cells.

    abstract::A growth cone-enriched fraction was prepared from 3-4 day rat cerebra. Examination of the growth cone fraction by electron microscopy revealed numerous structures circular in appearance that contain a number of features common to neuronal growth cones in vivo. The isolated growth cones stimulated a dose-dependent inco...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440050204

    authors: Dent EW,Ida JA Jr,Yoshino JE

    更新日期:1992-01-01 00:00:00

  • Calcium waves between astrocytes from Cx43 knockout mice.

    abstract::Gap junctions are regarded as the primary pathway underlying propagation of Ca2+ waves between astrocytes, although signaling through extracellular space may also contribute. Results obtained from astrocytes cultured from sibling Cx43 knockout (KO) and wild-type (WT) mice in six litters showed that Ca2+ waves propagat...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-1136(199809)24:1<65::aid-glia7>

    authors: Scemes E,Dermietzel R,Spray DC

    更新日期:1998-09-01 00:00:00

  • A functional role of NMDA receptor in regulating the differentiation of oligodendrocyte precursor cells and remyelination.

    abstract::Differentiation of oligodendrocyte precursor cells (OPCs) is the most important event for the myelination of central nervous system (CNS) axons during development and remyelination in demyelinating diseases, while the underlying molecular mechanisms remain largely unknown. Here we show that NMDA receptor (NMDAR) is a ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22469

    authors: Li C,Xiao L,Liu X,Yang W,Shen W,Hu C,Yang G,He C

    更新日期:2013-05-01 00:00:00

  • Enhanced connexin 43 immunoreactivity in penumbral areas in the human brain following ischemia.

    abstract::Astrocytes support neurons not only physically but also chemically by secreting neurotrophic factors and energy substrates. Moreover, astrocytes establish a glial network and communicate through gap junctions in the brain. Connexin 43 (Cx43) is one of major component proteins in astrocytic gap junctions. Heterozygote ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20399

    authors: Nakase T,Yoshida Y,Nagata K

    更新日期:2006-10-01 00:00:00

  • Astrocyte-targeted IL-10 production decreases proliferation and induces a downregulation of activated microglia/macrophages after PPT.

    abstract::When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin-10 (IL-10) h...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23573

    authors: Recasens M,Shrivastava K,Almolda B,González B,Castellano B

    更新日期:2019-04-01 00:00:00

  • Epidermal growth factor receptor expression regulates proliferation in the postnatal rat retina.

    abstract::Epidermal growth factor (EGF) is known to promote proliferation of both retinal progenitors and Muller glia in vitro, but several questions remain concerning an in vivo role for this factor. In this study, we investigated whether the EGF receptor (EGFR) is necessary for the maintenance of normal levels of progenitor a...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20361

    authors: Close JL,Liu J,Gumuscu B,Reh TA

    更新日期:2006-08-01 00:00:00

  • Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure.

    abstract::Inflammatory changes have been found in Parkinson's disease, in humans intoxicated with the parkinsonian toxin MPTP, and in animal models of the disease. However, it is still not known whether inflammatory changes are responsible for active nerve cell death or if they have a protective role against neurodegeneration. ...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20015

    authors: Barcia C,Sánchez Bahillo A,Fernández-Villalba E,Bautista V,Poza Y Poza M,Fernández-Barreiro A,Hirsch EC,Herrero MT

    更新日期:2004-05-01 00:00:00

  • Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    abstract::Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.23167

    authors: Schultz V,van der Meer F,Wrzos C,Scheidt U,Bahn E,Stadelmann C,Brück W,Junker A

    更新日期:2017-08-01 00:00:00

  • Astrocyte-specific expression of a soluble form of the murine complement control protein Crry confers demyelination protection in the cuprizone model.

    abstract::Complement has been implicated as a potential effector mechanism in neurodegeneration; yet the precise role of complement in this process remains elusive. In this report, we have utilized the cuprizone model of demyelination-remyelination to examine the contribution of complement to disease. C1q deposition was observe...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20551

    authors: Briggs DT,Martin CB,Ingersoll SA,Barnum SR,Martin BK

    更新日期:2007-11-01 00:00:00

  • Intrinsic optical signals in the rat optic nerve: role for K(+) uptake via NKCC1 and swelling of astrocytes.

    abstract::Measurements of extracellular space volume and imaging of intrinsic optical signals (IOSs) have shown that neuronal activity increases light transmittance by causing cellular swelling. However, the cellular mechanisms underlying these volume changes and the contribution of astrocyte swelling to the changes in tissue v...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10023

    authors: MacVicar BA,Feighan D,Brown A,Ransom B

    更新日期:2002-02-01 00:00:00

  • Neurofibromatosis 1 (NF1) heterozygosity results in a cell-autonomous growth advantage for astrocytes.

    abstract::Individuals with neurofibromatosis 1 (NF1) develop low-grade astrocytomas at an increased frequency. To gain insight into the function of the Nf1 gene product as a growth regulator for astrocytes, we examined mice heterozygous for a targeted Nf1 mutation. In our previous studies, we demonstrated increased numbers of p...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/1098-1136(20010315)33:4<314::aid-glia1030>

    authors: Bajenaru ML,Donahoe J,Corral T,Reilly KM,Brophy S,Pellicer A,Gutmann DH

    更新日期:2001-03-15 00:00:00

  • Microglia modulate respiratory rhythm generation and autoresuscitation.

    abstract::Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all p...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.22951

    authors: Lorea-Hernández JJ,Morales T,Rivera-Angulo AJ,Alcantara-Gonzalez D,Peña-Ortega F

    更新日期:2016-04-01 00:00:00

  • Focal adhesion kinase is required for endothelin-induced cell cycle progression of cultured astrocytes.

    abstract::When the brain is damaged, astrocytes often cause hyperplasia resulting in glial scar formation at the injured sites. Endothelins (ETs) have been shown to be involved in the pathophysiologic responses of astrocytes, including proliferation. In this study, we examined the mechanisms underlying the ET-induced astrocytic...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.10240

    authors: Koyama Y,Yoshioka Y,Matsuda T,Baba A

    更新日期:2003-08-01 00:00:00

  • AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy.

    abstract::We investigated the effect of receptor blockade induced by an angiotensin II type-1 receptor antagonist (AT(1)-RB) on glial and vascular changes in oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity (ROP). OIR was induced in Sprague-Dawley rats by exposure to 80% oxygen from postnatal (P) days 0-1...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.20680

    authors: Downie LE,Pianta MJ,Vingrys AJ,Wilkinson-Berka JL,Fletcher EL

    更新日期:2008-08-01 00:00:00

  • Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex.

    abstract::Atrial natriuretic peptide (ANP) represents a family of related peptides originally isolated from cardiac atria that have potent natriuretic, diuretic, and vasorelaxant properties. ANP has previously been localized in neurons of the rat brain in regions subserving cardiovascular functions and fluid/electrolyte balance...

    journal_title:Glia

    pub_type: 杂志文章

    doi:10.1002/glia.440120308

    authors: McKenzie JC,Berman NE,Thomas CR,Young JK,Compton LY,Cothran LN,Liu WL,Klein RM

    更新日期:1994-11-01 00:00:00

  • Adenosine dysfunction in epilepsy.

    abstract::Extracellular levels of the brain's endogenous anticonvulsant and neuroprotectant adenosine largely depend on an astrocyte-based adenosine cycle, comprised of ATP release, rapid degradation of ATP into adenosine, and metabolic reuptake of adenosine through equilibrative nucleoside transporters and phosphorylation by a...

    journal_title:Glia

    pub_type: 杂志文章,评审

    doi:10.1002/glia.22285

    authors: Boison D

    更新日期:2012-08-01 00:00:00