当前位置： SCI文献检索 > NEUROBIOLOGY OF DISEASE期刊下所有文献 > Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy.

Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy.

Abstract：

:Gephyrin is a postsynaptic scaffolding protein, essential for the clustering of glycine and γ-aminobutyric acid type-A receptors (GABAARs) at inhibitory synapses. An impairment of GABAergic synaptic inhibition represents a key pathway of epileptogenesis. Recently, exonic microdeletions in the gephyrin (GPHN) gene have been associated with neurodevelopmental disorders including autism spectrum disorder, schizophrenia and epileptic seizures. Here we report the identification of novel exonic GPHN microdeletions in two patients with idiopathic generalized epilepsy (IGE), representing the most common group of genetically determined epilepsies. The identified GPHN microdeletions involve exons 5-9 (Δ5-9) and 2-3 (Δ2-3), both affecting the gephyrin G-domain. Molecular characterization of the GPHN Δ5-9 variant demonstrated that it perturbs the clustering of regular gephyrin at inhibitory synapses in cultured mouse hippocampal neurons in a dominant-negative manner, resulting in a significant loss of γ2-subunit containing GABAARs. GPHN Δ2-3 causes a frameshift resulting in a premature stop codon (p.V22Gfs*7) leading to haplo-insufficiency of the gene. Our results demonstrate that structural exonic microdeletions affecting the GPHN gene constitute a rare genetic risk factor for IGE and other neuropsychiatric disorders by an impairment of the GABAergic inhibitory synaptic transmission.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Dejanovic B,Lal D,Catarino CB,Arjune S,Belaidi AA,Trucks H,Vollmar C,Surges R,Kunz WS,Motameny S,Altmüller J,Köhler A,Neubauer BA,Epicure Consortium,Nürnberg P,Noachtar S,Schwarz G,Sander T

doi

10.1016/j.nbd.2014.02.001

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

88-96

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(14)00036-9

journal_volume

67

pub_type

杂志文章

相关文献

NEUROBIOLOGY OF DISEASE文献大全
  • Astrocytic expression of the chaperone DNAJB6 results in non-cell autonomous protection in Huntington's disease.

    abstract：:Several neurodegenerative diseases like Huntington's, a polyglutamine (PolyQ) disease, are initiated by protein aggregation in neurons. Furthermore, these diseases are also associated with a multitude of responses in non-neuronal cells in the brain, in particular glial cells, like astrocytes. These non-neuronal respon...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2018.10.017

    authors： Bason M,Meister-Broekema M,Alberts N,Dijkers P,Bergink S,Sibon OCM,Kampinga HH

    更新日期：2019-04-01 00:00:00

  • Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia.

    abstract：:Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls. Quantitative endpoint RT-PCR was used to measure mRNA transcripts. Of the two enzymes capable of catalyzing the first step in the pathway, tryptophan 2,3-dioxygenase (TDO2) and indolea...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2003.12.015

    authors： Miller CL,Llenos IC,Dulay JR,Barillo MM,Yolken RH,Weis S

    更新日期：2004-04-01 00:00:00

  • The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease.

    abstract：:Huntington's disease (HD) is a devastating disorder that affects approximately 1 in 10,000 people and is accompanied by neuronal dysfunction and neurodegeneration. HD manifests as a progressive chorea, a decline in mental abilities accompanied by behavioural, emotional and psychiatric problems followed by, dementia, a...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章,评审

    doi：10.1016/j.nbd.2010.02.003

    authors： Buckley NJ,Johnson R,Zuccato C,Bithell A,Cattaneo E

    更新日期：2010-07-01 00:00:00

  • Effects of environmental manipulations in genetically targeted animal models of affective disorders.

    abstract：:Mental illness is the leading cause of disability worldwide. We are only just beginning to reveal and comprehend the complex interaction that exists between the genetic makeup of an organism and the potential modifying effect of the environment in which it lives, and how this translates into mediating susceptibility t...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章,评审

    doi：10.1016/j.nbd.2012.04.003

    authors： Renoir T,Pang TY,Hannan AJ

    更新日期：2013-09-01 00:00:00

  • Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1.

    abstract：:Cellular mechanisms play a role in conversion of the normal prion protein PrP(C) to the disease-associated protein PrP(Sc). The cells provide not only PrP(C), but also still largely undefined factors required for efficient prion replication. Previously, we have observed that interference with ERK and p38-JNK MAP kinas...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2013.05.014

    authors： Allard EK,Grujic M,Fisone G,Kristensson K

    更新日期：2013-10-01 00:00:00

  • Gene expression in the epileptic (EL) mouse hippocampus.

    abstract：:The neuropathology of hippocampal seizure foci in human temporal lobe epilepsy (TLE) and several animal models of epilepsy reveal extensive neuronal loss along with astrocyte and microglial activation. Studies of these models have advanced hypotheses that propose both pathological changes are essential for seizure gen...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2020.105152

    authors： Lee TS,Li AY,Rapuano A,Mantis J,Eid T,Seyfried TN,de Lanerolle NC

    更新日期：2021-01-01 00:00:00

  • Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA.

    abstract：:Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expr...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1006/nbdi.2001.0385

    authors： Schilling G,Jinnah HA,Gonzales V,Coonfield ML,Kim Y,Wood JD,Price DL,Li XJ,Jenkins N,Copeland N,Moran T,Ross CA,Borchelt DR

    更新日期：2001-06-01 00:00:00

  • Beta-amyloid controls altered Reelin expression and processing in Alzheimer's disease.

    abstract：:Reelin is a glycoprotein that modulates synaptic function and plasticity in the mature brain, thereby favouring memory formation. We recently reported altered cerebral Reelin expression in Alzheimer's disease (AD). Here we demonstrate pronounced Reelin changes at protein and mRNA levels in the frontal cortex in adult ...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2009.12.006

    authors： Botella-López A,Cuchillo-Ibáñez I,Cotrufo T,Mok SS,Li QX,Barquero MS,Dierssen M,Soriano E,Sáez-Valero J

    更新日期：2010-03-01 00:00:00

  • YOD1 attenuates neurogenic proteotoxicity through its deubiquitinating activity.

    abstract：:Ubiquitination, a fundamental post-translational modification of intracellular proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases). >90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses deubiquitinase activity and is similar to ovarian tumor domain-containing prote...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2018.01.006

    authors： Tanji K,Mori F,Miki Y,Utsumi J,Sasaki H,Kakita A,Takahashi H,Wakabayashi K

    更新日期：2018-04-01 00:00:00

  • T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motor behavior.

    abstract：:Adult-onset hypothyroidism is associated with neurological changes such as cognitive dysfunction and impaired learning, which may be related to alterations of synaptic plasticity. We investigate the consequence of adult-onset hypothyroidism on thyroid-mediated transcription events in striatal synaptic plasticity, and ...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2008.05.015

    authors： Vallortigara J,Alfos S,Micheau J,Higueret P,Enderlin V

    更新日期：2008-09-01 00:00:00

  • Subtle microstructural changes of the striatum in a DYT1 knock-in mouse model of dystonia.

    abstract：:The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brai...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2013.01.008

    authors： Song CH,Bernhard D,Bolarinwa C,Hess EJ,Smith Y,Jinnah HA

    更新日期：2013-06-01 00:00:00

  • Cystamine and intrabody co-treatment confers additional benefits in a fly model of Huntington's disease.

    abstract：:Huntington's disease (HD) is a lethal, neurodegenerative disorder caused by expansion of the polyglutamine repeat in the Huntingtin gene (HTT), leading to mutant protein misfolding, aggregation, and neuronal death. Feeding a Drosophila HD model cystamine, or expressing a transgene encoding the anti-htt intracellular a...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2010.04.007

    authors： Bortvedt SF,McLear JA,Messer A,Ahern-Rindell AJ,Wolfgang WJ

    更新日期：2010-10-01 00:00:00

  • Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice.

    abstract：:Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics an...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2015.02.031

    authors： Yue M,Hinkle KM,Davies P,Trushina E,Fiesel FC,Christenson TA,Schroeder AS,Zhang L,Bowles E,Behrouz B,Lincoln SJ,Beevers JE,Milnerwood AJ,Kurti A,McLean PJ,Fryer JD,Springer W,Dickson DW,Farrer MJ,Melrose HL

    更新日期：2015-06-01 00:00:00

  • Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.

    abstract：:We have studied the neurotoxicity of amyloid-beta (Abeta) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Abeta(1-42) compared to vehicle control an...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1006/nbdi.2002.0485

    authors： Walsh DT,Montero RM,Bresciani LG,Jen AY,Leclercq PD,Saunders D,EL-Amir AN,Gbadamoshi L,Gentleman SM,Jen LS

    更新日期：2002-06-01 00:00:00

  • Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease virus-infected brain is dependent upon inflammation.

    abstract：:Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected ra...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1006/nbdi.1998.0225

    authors： Röhrenbeck AM,Bette M,Hooper DC,Nyberg F,Eiden LE,Dietzschold B,Weihe E

    更新日期：1999-02-01 00:00:00

  • Correlation between cortical beta power and gait speed is suppressed in a parkinsonian model, but restored by therapeutic deep brain stimulation.

    abstract：:The motor cortex and subthalamic nucleus (STN) of patients with Parkinson's disease (PD) exhibit abnormally high levels of electrophysiological oscillations in the ~12-35 Hz beta-frequency range. Recent studies have shown that beta is partly carried forward to regulate future motor states in the healthy condition, sug...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2018.05.013

    authors： Polar CA,Gupta R,Lehmkuhle MJ,Dorval AD

    更新日期：2018-09-01 00:00:00

  • Psychosine induces the dephosphorylation of neurofilaments by deregulation of PP1 and PP2A phosphatases.

    abstract：:Patients with Krabbe disease, a genetic demyelinating syndrome caused by deficiency of galactosyl-ceramidase and the resulting accumulation of galactosyl-sphingolipids, develop signs of a dying-back axonopathy compounded by a deficiency of large-caliber axons. Here, we show that axonal caliber in Twitcher mice, an ani...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2012.01.013

    authors： Cantuti-Castelvetri L,Zhu H,Givogri MI,Chidavaenzi RL,Lopez-Rosas A,Bongarzone ER

    更新日期：2012-05-01 00:00:00

  • Unraveling substantia nigra sequential gene expression in a progressive MPTP-lesioned macaque model of Parkinson's disease.

    abstract：:Taking advantage of a progressive nonhuman primate model mimicking Parkinson's disease (PD) evolution, we monitored transcriptional fluctuations in the substantia nigra using Affymetrix microarrays in control (normal), saline-treated (normal), 6 days-treated (asymptomatic with 20% cell loss), 12 days-treated (asymptom...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2005.02.005

    authors： Bassilana F,Mace N,Li Q,Stutzmann JM,Gross CE,Pradier L,Benavides J,Ménager J,Bezard E

    更新日期：2005-10-01 00:00:00

  • Seasonal affective disorder and serotonin-related polymorphisms.

    abstract：:Disturbances in central serotonergic systems have been hypothesized to be involved in seasonal affective disorder (SAD). Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD patients ...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1006/nbdi.2000.0373

    authors： Johansson C,Smedh C,Partonen T,Pekkarinen P,Paunio T,Ekholm J,Peltonen L,Lichtermann D,Palmgren J,Adolfsson R,Schalling M

    更新日期：2001-04-01 00:00:00

  • Increased neuronal glutathione and neuroprotection in GTRAP3-18-deficient mice.

    abstract：:Glutathione (GSH) is an important neuroprotective molecule in the brain. The strategy to increase neuronal GSH level is a promising approach to the treatment of neurodegenerative diseases. However, the regulatory mechanism by which neuron-specific GSH synthesis is facilitated remains elusive. Glutamate transporter-ass...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2011.12.016

    authors： Aoyama K,Wang F,Matsumura N,Kiyonari H,Shioi G,Tanaka K,Kinoshita C,Kikuchi-Utsumi K,Watabe M,Nakaki T

    更新日期：2012-03-01 00:00:00

  • Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery.

    abstract：:We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater fun...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2007.01.012

    authors： Xiao M,Klueber KM,Guo Z,Lu C,Wang H,Roisen FJ

    更新日期：2007-05-01 00:00:00

  • Activation of caspase-1 dependent interleukins in developmental brain trauma.

    abstract：:Focal mechanical cortical trauma triggers diffuse apoptotic neurodegeneration in the developing rat brain which is associated with invasion of brain tissue with inflammatory mediators. We hypothesized that caspase-1 and the two caspase-1-processed cytokines, interleukin (IL)-1beta and IL-18, are involved in trauma-ind...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2006.11.003

    authors： Sifringer M,Stefovska V,Endesfelder S,Stahel PF,Genz K,Dzietko M,Ikonomidou C,Felderhoff-Mueser U

    更新日期：2007-03-01 00:00:00

  • Quantitative ultrasound and apoptotic death in the neonatal primate brain.

    abstract：:Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct struct...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2019.03.032

    authors： Rosado-Mendez IM,Noguchi KK,Castañeda-Martinez L,Kirvassilis G,Wang SH,Manzella F,Swiney BS,Masuoka K,Capuano S III2,Brunner KG,Crosno K,Guerrero QW,Whitson H,Brambrink A,Simmons HS,Mejia AF,Zagzebski JA,Hall TJ,Ikono

    更新日期：2019-07-01 00:00:00

  • Neuroprotective effects of erythropoietin in the rat hippocampus after pilocarpine-induced status epilepticus.

    abstract：:Neuroprotective functions of erythropoietin (Epo) are thought to involve a heteroreceptor composed of both Epo receptor (Epo-R) and common beta chain (betac). Here, we measured the response of hippocampal Epo system components (Epo, Epo-R and betac) during neurodegenerative processes following pilocarpine-induced stat...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2006.10.009

    authors： Nadam J,Navarro F,Sanchez P,Moulin C,Georges B,Laglaine A,Pequignot JM,Morales A,Ryvlin P,Bezin L

    更新日期：2007-02-01 00:00:00

  • Autism with seizures and intellectual disability: possible causative role of gain-of-function of the inwardly-rectifying K+ channel Kir4.1.

    abstract：:The inwardly-rectifying potassium channel Kir4.1 is a major player in the astrocyte-mediated regulation of [K(+)](o) in the brain, which is essential for normal neuronal activity and synaptic functioning. KCNJ10, encoding Kir4.1, has been recently linked to seizure susceptibility in humans and mice, and is a possible ...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2011.03.016

    authors： Sicca F,Imbrici P,D'Adamo MC,Moro F,Bonatti F,Brovedani P,Grottesi A,Guerrini R,Masi G,Santorelli FM,Pessia M

    更新日期：2011-07-01 00:00:00

  • Death of motoneurons induced by trophic deprivation or by excitotoxicity is not prevented by overexpression of SMN.

    abstract：:The telomeric copy of the survival motor neuron gene (SMN1) is deleted or mutated in all spinal muscular atrophy (SMA) patients and these patients present mainly a loss in spinal motoneurons. Although studies performed in HeLa cells suggest that SMN may be involved in the biogenesis and possibly in recycling of splice...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1006/nbdi.2000.0374

    authors： Cisterni C,Kallenbach S,Jordier F,Bagnis C,Pettmann B

    更新日期：2001-04-01 00:00:00

  • Alzheimer's disease pathology in APOE transgenic mouse models: The Who, What, When, Where, Why, and How.

    abstract：:The focus on amyloid plaques and neurofibrillary tangles has yielded no Alzheimer's disease (AD) modifying treatments in the past several decades, despite successful studies in preclinical mouse models. This inconsistency has caused a renewed focus on improving the fidelity and reliability of AD mouse models, with dis...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章,评审

    doi：10.1016/j.nbd.2020.104811

    authors： Lewandowski CT,Maldonado Weng J,LaDu MJ

    更新日期：2020-06-01 00:00:00

  • Modulation of serotonin dynamics in the dorsal raphe nucleus via high frequency medial prefrontal cortex stimulation.

    abstract：:The subcallosal cingulate (SCC) region, or its rodent homologue the medial prefrontal cortex (mPFC), and midbrain dorsal raphe (DR) are crucial nodes of the widespread network implicated in emotional regulation. Stimulation of the SCC is being explored as a potential treatment for depression. Because modulation of the...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2016.06.009

    authors： Srejic LR,Wood KM,Zeqja A,Hashemi P,Hutchison WD

    更新日期：2016-10-01 00:00:00

  • Decorin blocks scarring and cystic cavitation in acute and induces scar dissolution in chronic spinal cord wounds.

    abstract：:In the injured central nervous system (CNS), transforming growth factor (TGF)-β1/2-induced scarring and wound cavitation impede axon regeneration implying that a combination of both scar suppression and axogenic treatments is required to achieve functional recovery. After treating acute and chronic dorsal funicular sp...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2013.12.008

    authors： Ahmed Z,Bansal D,Tizzard K,Surey S,Esmaeili M,Gonzalez AM,Berry M,Logan A

    更新日期：2014-04-01 00:00:00

  • Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6.

    abstract：:Oxidative stress and protein aggregation are biochemical hallmarks of Parkinson's disease (PD), a frequent sporadic late-onset degenerative disorder particularly of dopaminergic neurons in the substantia nigra, resulting in impaired spontaneous movement. PARK6 is a rare autosomal-recessively inherited disorder, mimick...

    journal_title：Neurobiology of disease

    pub_type： 杂志文章

    doi：10.1016/j.nbd.2006.10.007

    authors： Hoepken HH,Gispert S,Morales B,Wingerter O,Del Turco D,Mülsch A,Nussbaum RL,Müller K,Dröse S,Brandt U,Deller T,Wirth B,Kudin AP,Kunz WS,Auburger G

    更新日期：2007-02-01 00:00:00