Functional changes in glutamate transporters and astrocyte biophysical properties in a rodent model of focal cortical dysplasia.

Abstract:

:Cortical dysplasia is associated with intractable epilepsy and developmental delay in young children. Recent work with the rat freeze-induced focal cortical dysplasia (FCD) model has demonstrated that hyperexcitability in the dysplastic cortex is due in part to higher levels of extracellular glutamate. Astrocyte glutamate transporters play a pivotal role in cortical maintaining extracellular glutamate concentrations. Here we examined the function of astrocytic glutamate transporters in a FCD model in rats. Neocortical freeze lesions were made in postnatal day (PN) 1 rat pups and whole cell electrophysiological recordings and biochemical studies were performed at PN 21-28. Synaptically evoked glutamate transporter currents in astrocytes showed a near 10-fold reduction in amplitude compared to sham operated controls. Astrocyte glutamate transporter currents from lesioned animals were also significantly reduced when challenged exogenously applied glutamate. Reduced astrocytic glutamate transport clearance contributed to increased NMDA receptor-mediated current decay kinetics in lesioned animals. The electrophysiological profile of astrocytes in the lesion group was also markedly changed compared to sham operated animals. Control astrocytes demonstrate large-amplitude linear leak currents in response to voltage-steps whereas astrocytes in lesioned animals demonstrated significantly smaller voltage-activated inward and outward currents. Significant decreases in astrocyte resting membrane potential and increases in input resistance were observed in lesioned animals. However, Western blotting, immunohistochemistry and quantitative PCR demonstrated no differences in the expression of the astrocytic glutamate transporter GLT-1 in lesioned animals relative to controls. These data suggest that, in the absence of changes in protein or mRNA expression levels, functional changes in astrocytic glutamate transporters contribute to neuronal hyperexcitability in the FCD model.

journal_name

Front Cell Neurosci

authors

Campbell SL,Hablitz JJ,Olsen ML

doi

10.3389/fncel.2014.00425

subject

Has Abstract

pub_date

2014-12-17 00:00:00

pages

425

issn

1662-5102

journal_volume

8

pub_type

杂志文章
  • Mechanisms of Homeostatic Synaptic Plasticity in vivo.

    abstract::Synapses undergo rapid activity-dependent plasticity to store information, which when left uncompensated can lead to destabilization of neural function. It has been well documented that homeostatic changes, which operate at a slower time scale, are required to maintain stability of neural networks. While there are man...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2019.00520

    authors: Lee HK,Kirkwood A

    更新日期:2019-12-03 00:00:00

  • Bilateral Synchronization of Hippocampal Early Sharp Waves in Neonatal Rats.

    abstract::In the neonatal rodent hippocampus, the first and predominant pattern of correlated neuronal network activity is early sharp waves (eSPWs). Whether and how eSPWs are organized bilaterally remains unknown. Here, using simultaneous silicone probe recordings from the left and right hippocampus in neonatal rats in vivo we...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00029

    authors: Valeeva G,Nasretdinov A,Rychkova V,Khazipov R

    更新日期:2019-02-07 00:00:00

  • The Molecular Determinants of Mitochondrial Membrane Contact With ER, Lysosomes and Peroxisomes in Neuronal Physiology and Pathology.

    abstract::Membrane tethering is an important communication method for membrane-packaged organelles. Mitochondria are organelles with a bilayer membrane, and the membrane contact between mitochondria and other organelles is indispensable for maintaining cellular homeostasis. Increased levels of molecular determinants that mediat...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.00194

    authors: Liao Y,Dong Y,Cheng J

    更新日期:2020-08-07 00:00:00

  • Transduction of Adeno-Associated Virus Vectors Targeting Hair Cells and Supporting Cells in the Neonatal Mouse Cochlea.

    abstract::Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expres...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00008

    authors: Gu X,Chai R,Guo L,Dong B,Li W,Shu Y,Huang X,Li H

    更新日期:2019-01-24 00:00:00

  • Effects of low frequency electric fields on synaptic integration in hippocampal CA1 pyramidal neurons: implications for power line emissions.

    abstract::The possible cognitive effects of low frequency external electric fields (EFs), such as those generated by power lines, are poorly understood. Their functional consequences for mechanisms at the single neuron level are very difficult to study and identify experimentally, especially in vivo. The major open problem is t...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00310

    authors: Cavarretta F,Carnevale NT,Tegolo D,Migliore M

    更新日期:2014-10-09 00:00:00

  • GnRH-1 Neural Migration From the Nose to the Brain Is Independent From Slit2, Robo3 and NELL2 Signaling.

    abstract::Gonadotropin releasing hormone-1 (GnRH-1) neurons play a pivotal role in controlling pubertal onset and fertility once they reach their hypothalamic location. During embryonic development, GnRH-1 neurons migrate from the nasal area to the hypothalamus where they modulate gonadotropin release from the pituitary gland. ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00070

    authors: Taroc EZM,Lin JM,Tulloch AJ,Jaworski A,Forni PE

    更新日期:2019-03-01 00:00:00

  • The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging.

    abstract::The subventricular zone (SVZ) is the largest source of newly generated cells in the adult mammalian brain. SVZ-derived neuroblasts migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into mature neurons. Additionally, a small proportion of SVZ-derived cells contribute to...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2013.00147

    authors: Capilla-Gonzalez V,Cebrian-Silla A,Guerrero-Cazares H,Garcia-Verdugo JM,Quiñones-Hinojosa A

    更新日期:2013-09-11 00:00:00

  • Flexor and Extensor Ankle Afferents Broadly Innervate Locomotor Spinal Shox2 Neurons and Induce Similar Effects in Neonatal Mice.

    abstract::Central pattern generators (CPGs) in the thoracolumbar spinal cord generate the basic hindlimb locomotor pattern. The locomotor CPG integrates descending commands and sensory information from the periphery to activate, modulate and halt the rhythmic program. General CPG function and response to sensory perturbations a...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00452

    authors: Li EZ,Garcia-Ramirez DL,Dougherty KJ

    更新日期:2019-10-09 00:00:00

  • The Tripeptide RER Mimics Secreted Amyloid Precursor Protein-Alpha in Upregulating LTP.

    abstract::Secreted amyloid precursor protein-alpha (sAPPα), generated by enzymatic processing of the APP, possesses a range of neurotrophic and neuroprotective properties and plays a critical role in the molecular mechanisms of memory and learning. One of the key active regions of sAPPα is the central APP domain (E2) that conta...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00459

    authors: Morrissey JA,Bigus E,Necarsulmer JC,Srinivasan V,Peppercorn K,O'Leary DJ,Mockett BG,Tate WP,Hughes SM,Parfitt KD,Abraham WC

    更新日期:2019-10-18 00:00:00

  • An epigenetic hypothesis for the genomic memory of pain.

    abstract::Chronic pain is accompanied with long-term sensory, affective and cognitive disturbances. What are the mechanisms that mediate the long-term consequences of painful experiences and embed them in the genome? We hypothesize that alterations in DNA methylation, an enzymatic covalent modification of cytosine bases in DNA,...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2015.00088

    authors: Alvarado S,Tajerian M,Suderman M,Machnes Z,Pierfelice S,Millecamps M,Stone LS,Szyf M

    更新日期:2015-03-24 00:00:00

  • Molecular and Functional Characterization of Neurogenin-2 Induced Human Sensory Neurons.

    abstract::Sensory perception is fundamental to everyday life, yet understanding of human sensory physiology at the molecular level is hindered due to constraints on tissue availability. Emerging strategies to study and characterize peripheral neuropathies in vitro involve the use of human pluripotent stem cells (hPSCs) differen...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.600895

    authors: Hulme AJ,McArthur JR,Maksour S,Miellet S,Ooi L,Adams DJ,Finol-Urdaneta RK,Dottori M

    更新日期:2020-12-04 00:00:00

  • MEA6 Deficiency Impairs Cerebellar Development and Motor Performance by Tethering Protein Trafficking.

    abstract::Meningioma expressed antigen 6 (MEA6), also called cutaneous T cell lymphoma-associated antigen 5 (cTAGE5), was initially found in tumor tissues. MEA6 is located in endoplasmic reticulum (ER) exit sites and regulates the transport of collagen, very low density lipoprotein, and insulin. It is also reported that MEA6 mi...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00250

    authors: Wang XT,Cai XY,Xu FX,Zhou L,Zheng R,Ma KY,Xu ZH,Shen Y

    更新日期:2019-06-11 00:00:00

  • The pivotal role of astrocytes in an in vitro stroke model of the blood-brain barrier.

    abstract::Stabilization of the blood-brain barrier during and after stroke can lead to less adverse outcome. For elucidation of underlying mechanisms and development of novel therapeutic strategies validated in vitro disease models of the blood-brain barrier could be very helpful. To mimic in vitro stroke conditions we have est...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00352

    authors: Neuhaus W,Gaiser F,Mahringer A,Franz J,Riethmüller C,Förster C

    更新日期:2014-10-28 00:00:00

  • Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves.

    abstract::The pannexin family of channels consists of three members-pannexin-1 (Panx1), pannexin-2 (Panx2), and pannexin-3 (Panx3) that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00365

    authors: Horton SM,Luna Lopez C,Blevins E,Howarth H,Weisberg J,Shestopalov VI,Makarenkova HP,Shah SB

    更新日期:2017-11-22 00:00:00

  • Aβ and Inflammatory Stimulus Activate Diverse Signaling Pathways in Monocytic Cells: Implications in Retaining Phagocytosis in Aβ-Laden Environment.

    abstract::Background: Accumulation of amyloid β (Aβ) is one of the main hallmarks of Alzheimer's disease (AD). The enhancement of Aβ clearance may provide therapeutic means to restrict AD pathology. The cellular responses to different forms of Aβ in monocytic cells are poorly known. We aimed to study whether different forms of ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2016.00279

    authors: Savchenko E,Malm T,Konttinen H,Hämäläinen RH,Guerrero-Toro C,Wojciechowski S,Giniatullin R,Koistinaho J,Magga J

    更新日期:2016-12-05 00:00:00

  • Brain immune cell composition and functional outcome after cerebral ischemia: comparison of two mouse strains.

    abstract::Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stro...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2014.00365

    authors: Kim HA,Whittle SC,Lee S,Chu HX,Zhang SR,Wei Z,Arumugam TV,Vinh A,Drummond GR,Sobey CG

    更新日期:2014-11-19 00:00:00

  • Early Developmental Marginal Zinc Deficiency Affects Neurogenesis Decreasing Neuronal Number and Altering Neuronal Specification in the Adult Rat Brain.

    abstract::During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulate...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00062

    authors: Adamo AM,Liu X,Mathieu P,Nuttall JR,Supasai S,Oteiza PI

    更新日期:2019-03-01 00:00:00

  • Sensory transduction at the frog semicircular canal: how hair cell membrane potential controls junctional transmission.

    abstract::At the frog semicircular canals, the afferent fibers display high spontaneous activity (mEPSPs), due to transmitter release from hair cells. mEPSP and spike frequencies are modulated by stimulation that activates the hair cell receptor conductance. The relation between receptor current and transmitter release cannot b...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2015.00235

    authors: Martini M,Canella R,Rubbini G,Fesce R,Rossi ML

    更新日期:2015-06-23 00:00:00

  • FUS Mislocalization and Vulnerability to DNA Damage in ALS Patients Derived hiPSCs and Aging Motoneurons.

    abstract::Mutations within the FUS gene (Fused in Sarcoma) are known to cause Amyotrophic Lateral Sclerosis (ALS), a neurodegenerative disease affecting upper and lower motoneurons. The FUS gene codes for a multifunctional RNA/DNA-binding protein that is primarily localized in the nucleus and is involved in cellular processes s...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2016.00290

    authors: Higelin J,Demestre M,Putz S,Delling JP,Jacob C,Lutz AK,Bausinger J,Huber AK,Klingenstein M,Barbi G,Speit G,Huebers A,Weishaupt JH,Hermann A,Liebau S,Ludolph AC,Boeckers TM

    更新日期:2016-12-26 00:00:00

  • Visualization of cyclic nucleotide dynamics in neurons.

    abstract::The second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) transduce many neuromodulatory signals from hormones and neurotransmitters into specific functional outputs. Their production, degradation and signaling are spatiotemporally regulated to achieve high specificity in si...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2014.00395

    authors: Gorshkov K,Zhang J

    更新日期:2014-12-04 00:00:00

  • Differential Regulation of Adhesion and Phagocytosis of Resting and Activated Microglia by Dopamine.

    abstract::Microglia, the immune competent cells of the central nervous system (CNS), normally exist in a resting state characterized by a ramified morphology with many processes, and become activated to amoeboid morphology in response to brain injury, infection, and a variety of neuroinflammatory stimuli. Many studies focused o...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2018.00309

    authors: Fan Y,Chen Z,Pathak JL,Carneiro AMD,Chung CY

    更新日期:2018-09-11 00:00:00

  • Impaired NGF/TrkA Signaling Causes Early AD-Linked Presynaptic Dysfunction in Cholinergic Primary Neurons.

    abstract::Alterations in NGF/TrkA signaling have been suggested to underlie the selective degeneration of the cholinergic basal forebrain neurons occurring in vivo in AD (Counts and Mufson, 2005; Mufson et al., 2008; Niewiadomska et al., 2011) and significant reduction of cognitive decline along with an improvement of cholinerg...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00068

    authors: Latina V,Caioli S,Zona C,Ciotti MT,Amadoro G,Calissano P

    更新日期:2017-03-15 00:00:00

  • Profiles of VGF Peptides in the Rat Brain and Their Modulations after Phencyclidine Treatment.

    abstract::From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence,...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00158

    authors: Noli B,Sanna F,Brancia C,D'Amato F,Manconi B,Vincenzoni F,Messana I,Melis MR,Argiolas A,Ferri GL,Cocco C

    更新日期:2017-06-02 00:00:00

  • Antagonization of the Nogo-Receptor 1 Enhances Dopaminergic Fiber Outgrowth of Transplants in a Rat Model of Parkinson's Disease.

    abstract::Intrastriatal transplantation of fetal human ventral mesencephalic dopaminergic neurons is an experimental therapy for patients suffering from Parkinson's disease. The success of this approach depends on several host brain parameters including neurotrophic factors and growth inhibitors that guide survival and integrat...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2017.00151

    authors: Seiler S,Di Santo S,Andereggen L,Widmer HR

    更新日期:2017-05-26 00:00:00

  • Optimization of Efficient Neuron Models With Realistic Firing Dynamics. The Case of the Cerebellar Granule Cell.

    abstract::Biologically relevant large-scale computational models currently represent one of the main methods in neuroscience for studying information processing primitives of brain areas. However, biologically realistic neuron models tend to be computationally heavy and thus prevent these models from being part of brain-area mo...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.00161

    authors: Marín M,Sáez-Lara MJ,Ros E,Garrido JA

    更新日期:2020-07-14 00:00:00

  • Reward-Related Behavioral, Neurochemical and Electrophysiological Changes in a Rat Model of Autism Based on Prenatal Exposure to Valproic Acid.

    abstract::Prenatal exposure to the antiepileptic drug valproic acid (VPA) induces autism spectrum disorder (ASD) in humans and autistic-like behaviors in rodents, which makes it a good model to study the neural underpinnings of ASD. Rats prenatally exposed to VPA show profound deficits in the social domain. The altered social b...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2019.00479

    authors: Schiavi S,Iezzi D,Manduca A,Leone S,Melancia F,Carbone C,Petrella M,Mannaioni G,Masi A,Trezza V

    更新日期:2019-10-25 00:00:00

  • Long Term Gene Expression in Human Induced Pluripotent Stem Cells and Cerebral Organoids to Model a Neurodegenerative Disease.

    abstract::Human brain organoids (mini-brains) consist of self-organized three-dimensional (3D) neural tissue which can be derived from reprogrammed adult cells and maintained for months in culture. These 3D structures manifest substantial potential for the modeling of neurodegenerative diseases and pave the way for personalized...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.00014

    authors: Nassor F,Jarray R,Biard DSF,Maïza A,Papy-Garcia D,Pavoni S,Deslys JP,Yates F

    更新日期:2020-02-11 00:00:00

  • Phase Coupled Firing of Prefrontal Parvalbumin Interneuron With High Frequency Oscillations.

    abstract::The prefrontal cortex (PFC) plays a central role in executive functions and inhibitory control over many cognitive behaviors. Dynamic changes in local field potentials (LFPs), such as gamma oscillation, have been hypothesized to be important for attentive behaviors and modulated by local interneurons such as parvalbum...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fncel.2020.610741

    authors: Yao Y,Wu M,Wang L,Lin L,Xu J

    更新日期:2020-11-25 00:00:00

  • A17 Amacrine Cells and Olfactory Granule Cells: Parallel Processors of Early Sensory Information.

    abstract::Neurons typically receive synaptic input in their dendritic arbor, integrate inputs in their soma, and send output action potentials through their axon, following Cajal's law of dynamic polarization. Two notable exceptions are retinal amacrine cells and olfactory granule cells (GCs), which flout Cajal's edict by provi...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2020.600537

    authors: Egger V,Diamond JS

    更新日期:2020-11-05 00:00:00

  • Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation.

    abstract::Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular ...

    journal_title:Frontiers in cellular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fncel.2016.00129

    authors: Wang YF,Parpura V

    更新日期:2016-05-13 00:00:00