Soluble Aβ oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance.

Abstract:

:Epileptic activity may be more prevalent in early stage Alzheimer's disease (AD) than previously believed. Several studies report spontaneous seizures and interictal discharges in mouse models of AD undergoing age-related Aβ accumulation. The mechanism by which Aβ-induced neuronal excitability can trigger epileptiform activity remains unknown. Here, we systematically examined field excitatory postsynaptic potentials (fEPSP) in stratum radiatum and population spikes (PSs) in the adjacent stratum pyramidale of CA1 in wild-type mouse hippocampal slices. Soluble Aβ oligomers (oAβ) blocked hippocampal LTP and EPSP-spike (E-S) potentiation, and these effects were occluded by prior treatment with the glutamate uptake inhibitor TBOA. In accord, oAβ elevated glutamate levels in the hippocampal slice medium. Recording the PS revealed that oAβ increased PS frequency and reduced LTP, and this LTP deficit was occluded by pretreatment with the GABAA antagonist picrotoxin. Whole-cell recordings showed that oAβ significantly increased spontaneous EPSC frequency. Decreasing neuronal activity by increasing GABA tone or partially blocking NMDAR activity prevented oAβ impairment of hippocampal LTP. Finally, treating slices with two antiepileptic drugs rescued the LTP inhibition induced by oAβ. We conclude that soluble Aβ oligomers at the low nanomolar levels present in AD brain increase neuronal excitability by disrupting glutamatergic/GABAergic balance, thereby impairing synaptic plasticity.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Lei M,Xu H,Li Z,Wang Z,O'Malley TT,Zhang D,Walsh DM,Xu P,Selkoe DJ,Li S

doi

10.1016/j.nbd.2015.10.019

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

111-121

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(15)30077-2

journal_volume

85

pub_type

杂志文章
  • Impaired ATF6α processing, decreased Rheb and neuronal cell cycle re-entry in Huntington's disease.

    abstract::The endoplasmic reticulum-stress response is induced in several neurodegenerative diseases and in cellular models of Huntington's disease. However, here we report that the processing of ATF6α to its active nuclear form, one of the three branches of endoplasmic reticulum-stress activation, is impaired in both animal mo...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2010.08.014

    authors: Fernandez-Fernandez MR,Ferrer I,Lucas JJ

    更新日期:2011-01-01 00:00:00

  • Glia: victims or villains of the aging brain?

    abstract::Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2020.105008

    authors: Salas IH,Burgado J,Allen NJ

    更新日期:2020-09-01 00:00:00

  • Proximal movements compensate for distal forelimb movement impairments in a reach-to-eat task in Huntington's disease: new insights into motor impairments in a real-world skill.

    abstract::Huntington's disease (HD) causes severe motor impairments that are characterized by chorea, dystonia, and impaired fine motor control. The motor deficits include deficits in the control of the forelimb, but as yet there has been no comprehensive assessment of the impairments in arm, hand and digit movements as they ar...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2010.11.002

    authors: Klein A,Sacrey LA,Dunnett SB,Whishaw IQ,Nikkhah G

    更新日期:2011-02-01 00:00:00

  • DJ-1 associates with synaptic membranes.

    abstract::Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons. Although many reports have suggested that genetic factors are implicated in the pathogenesis of PD, molecular mechanisms underlying selective dopaminergic neuronal degeneration remain unknown. DJ-1 is a causative gene for ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.05.014

    authors: Usami Y,Hatano T,Imai S,Kubo S,Sato S,Saiki S,Fujioka Y,Ohba Y,Sato F,Funayama M,Eguchi H,Shiba K,Ariga H,Shen J,Hattori N

    更新日期:2011-09-01 00:00:00

  • The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model.

    abstract::Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. T...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.01.002

    authors: Ezzatizadeh V,Pinto RM,Sandi C,Sandi M,Al-Mahdawi S,Te Riele H,Pook MA

    更新日期:2012-04-01 00:00:00

  • Heritability and genetic variance of dementia with Lewy bodies.

    abstract::Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of comp...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2019.04.004

    authors: Guerreiro R,Escott-Price V,Hernandez DG,Kun-Rodrigues C,Ross OA,Orme T,Neto JL,Carmona S,Dehghani N,Eicher JD,Shepherd C,Parkkinen L,Darwent L,Heckman MG,Scholz SW,Troncoso JC,Pletnikova O,Dawson T,Rosenthal L,Ansor

    更新日期:2019-07-01 00:00:00

  • Pyruvate incubation enhances glycogen stores and sustains neuronal function during subsequent glucose deprivation.

    abstract::The use of energy substrates, such as lactate and pyruvate, has been shown to improve synaptic function when administered during glucose deprivation. In the present study, we investigated whether prolonged incubation with monocarboxylate (pyruvate or lactate) prior rather than during glucose deprivation can also susta...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2011.08.002

    authors: Shetty PK,Sadgrove MP,Galeffi F,Turner DA

    更新日期:2012-01-01 00:00:00

  • Alpha-synuclein and transgenic mouse models.

    abstract::Identified as the cause of some familial forms of Parkinson disease (PD) and as one of the major component of Lewy bodies, alpha-synuclein (alpha-syn) became the molecular hallmark of several neurodegenerative conditions now designated as synucleinopathies. Transgenic models have been generated to elucidate its physio...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2004.07.001

    authors: Fernagut PO,Chesselet MF

    更新日期:2004-11-01 00:00:00

  • Gene co-expression networks shed light into diseases of brain iron accumulation.

    abstract::Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whe...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2015.12.004

    authors: Bettencourt C,Forabosco P,Wiethoff S,Heidari M,Johnstone DM,Botía JA,Collingwood JF,Hardy J,UK Brain Expression Consortium (UKBEC).,Milward EA,Ryten M,Houlden H

    更新日期:2016-03-01 00:00:00

  • Frataxin shows developmentally regulated tissue-specific expression in the mouse embryo.

    abstract::Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease caused either by an intronic GAA triplet repeat expansion that suppresses the expression of the frataxin gene on chromosome 9q13, or, rarely, by point mutations in the frataxin gene. We investigated the expression of the mouse frataxin homologue d...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.1997.0139

    authors: Jiralerspong S,Liu Y,Montermini L,Stifani S,Pandolfo M

    更新日期:1997-01-01 00:00:00

  • Characterisation of cytoskeletal abnormalities in mice transgenic for wild-type human tau and familial Alzheimer's disease mutants of APP and presenilin-1.

    abstract::To study the role of Abeta amyloid deposits in the generation of cytoskeletal lesions, we have generated a transgenic mouse line coexpressing in the same neurons a wild-type human tau isoform (0N3R), a mutant form of APP (751SL) and a mutant form of PS1 (M146L). These mice developed early cerebral extracellular deposi...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2003.09.007

    authors: Boutajangout A,Authelet M,Blanchard V,Touchet N,Tremp G,Pradier L,Brion JP

    更新日期:2004-02-01 00:00:00

  • Cerebrovascular pathology during the progression of experimental Alzheimer's disease.

    abstract::Clinical and experimental evidence point to a possible role of cerebrovascular dysfunction in Alzheimer's disease (AD). The 5xFAD mouse model of AD expresses human amyloid precursor protein and presenilin genes with mutations found in AD patients. It remains unknown whether amyloid deposition driven by these mutations...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2016.01.001

    authors: Giannoni P,Arango-Lievano M,Neves ID,Rousset MC,Baranger K,Rivera S,Jeanneteau F,Claeysen S,Marchi N

    更新日期:2016-04-01 00:00:00

  • Adolescent cannabis exposure interacts with mutant DISC1 to produce impaired adult emotional memory.

    abstract::Cannabis is an increasingly popular and controversial drug used worldwide. Cannabis use often begins during adolescence, a highly susceptible period for environmental stimuli to alter functional and structural organization of the developing brain. Given that adolescence is a critical time for the emergence of mental i...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2015.06.006

    authors: Ballinger MD,Saito A,Abazyan B,Taniguchi Y,Huang CH,Ito K,Zhu X,Segal H,Jaaro-Peled H,Sawa A,Mackie K,Pletnikov MV,Kamiya A

    更新日期:2015-10-01 00:00:00

  • Formoterol, a β2-adrenoreceptor agonist, induces mitochondrial biogenesis and promotes cognitive recovery after traumatic brain injury.

    abstract::Traumatic brain injury (TBI) leads to acute necrosis at the site of injury followed by a sequence of secondary events lasting from hours to weeks and often years. Targeting mitochondrial impairment following TBI has shown improvements in brain mitochondrial bioenergetics and neuronal function. Recently formoterol, a h...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2020.104866

    authors: Vekaria HJ,Hubbard WB,Scholpa NE,Spry ML,Gooch JL,Prince SJ,Schnellmann RG,Sullivan PG

    更新日期:2020-07-01 00:00:00

  • The vasculature as a neural stem cell niche.

    abstract::Neural stem cells (NSCs) are multipotent, self-renewing progenitors that generate progeny that differentiate into neurons and glia. NSCs in the adult mammalian brain are generally quiescent. Environmental stimuli such as learning or exercise can activate quiescent NSCs, inducing them to proliferate and produce new neu...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2017.01.010

    authors: Otsuki L,Brand AH

    更新日期:2017-11-01 00:00:00

  • Developmental expression of GPR3 in rodent cerebellar granule neurons is associated with cell survival and protects neurons from various apoptotic stimuli.

    abstract::G-protein coupled receptor 3 (GPR3), GPR6, and GPR12 belong to a family of constitutively active Gs-coupled receptors that activate 3'-5'-cyclic adenosine monophosphate (cAMP) and are highly expressed in the brain. Among these receptors, the endogenous expression of GPR3 in cerebellar granule neurons (CGNs) is increas...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2014.04.007

    authors: Tanaka S,Miyagi T,Dohi E,Seki T,Hide I,Sotomaru Y,Saeki Y,Antonio Chiocca E,Matsumoto M,Sakai N

    更新日期:2014-08-01 00:00:00

  • Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.

    abstract::To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significan...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2010.06.007

    authors: Harris VK,Diamanduros A,Good P,Zakin E,Chalivendra V,Sadiq SA

    更新日期:2010-10-01 00:00:00

  • Neuroprotective effects of the Sigma-1 receptor (S1R) agonist PRE-084, in a mouse model of motor neuron disease not linked to SOD1 mutation.

    abstract::The identification of novel molecular targets crucially involved in motor neuron degeneration/survival is a necessary step for the development of hopefully more effective therapeutic strategies for amyotrophic lateral sclerosis (ALS) patients. In this view, S1R, an endoplasmic reticulum (ER)-resident receptor with cha...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.10.010

    authors: Peviani M,Salvaneschi E,Bontempi L,Petese A,Manzo A,Rossi D,Salmona M,Collina S,Bigini P,Curti D

    更新日期:2014-02-01 00:00:00

  • MicroRNA dysregulation in schizophrenia.

    abstract::Schizophrenia is a complex neuropsychiatric disorder that involves disturbances in neural circuitry and synaptic function. The exquisite network architecture and capacity for discreet post-synaptic remodeling of neurons requires coordination by an elaborate intracellular network of molecular signal transduction system...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2011.12.029

    authors: Beveridge NJ,Cairns MJ

    更新日期:2012-05-01 00:00:00

  • Interaction of ASK1 and the beta-amyloid precursor protein in a stress-signaling complex.

    abstract::The amyloid precursor protein (APP) is a type I transmembrane protein translocated to neuronal terminals, whose function is still unknown. The C-terminus of APP mediates its interaction with cellular adaptor and signaling proteins, some of which signal to the stress-activated protein kinase (SAPK) pathway. Here we sho...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2007.06.017

    authors: Galvan V,Banwait S,Spilman P,Gorostiza OF,Peel A,Ataie M,Crippen D,Huang W,Sidhu G,Ichijo H,Bredesen DE

    更新日期:2007-10-01 00:00:00

  • Active immunization trial in Abeta42-injected P301L tau transgenic mice.

    abstract::Amyloid beta-peptide (Abeta) containing plaques and neurofibrillary tangles (NFT) are the two major histopathological hallmarks of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, deposition of Abeta is an initial and essential step in the pathogenesis of AD, and formation of NFT has been propose...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2005.10.002

    authors: Kulic L,Kurosinski P,Chen F,Tracy J,Mohajeri MH,Li H,Nitsch RM,Götz J

    更新日期:2006-04-01 00:00:00

  • Activation of the neuronal c-Abl tyrosine kinase by amyloid-beta-peptide and reactive oxygen species.

    abstract::The deposition and accumulation of amyloid-beta-peptide (Abeta) in the brain are considered a sine qua non for Alzheimer's disease. The experimental delivery of fibrilized Abeta serves as a cellular model for several facets of the disease including the induction of synaptic dysfunction and apoptosis. c-Abl kinase is i...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2004.06.007

    authors: Alvarez AR,Sandoval PC,Leal NR,Castro PU,Kosik KS

    更新日期:2004-11-01 00:00:00

  • Neurostimulation techniques to enhance sleep and improve cognition in aging.

    abstract::Sleep plays a critical role in the process of memory consolidation. In particular, during non-rapid eye movement (NREM) slow wave sleep, slow-oscillations, spindles, hippocampal sharp wave ripples, and their phase coupling are involved in the process of transferring and consolidating information recently encoded and t...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章,评审

    doi:10.1016/j.nbd.2020.104865

    authors: Grimaldi D,Papalambros NA,Zee PC,Malkani RG

    更新日期:2020-07-01 00:00:00

  • Glut1 deficiency (G1D): epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype.

    abstract::Brain glucose supplies most of the carbon required for acetyl-coenzyme A (acetyl-CoA) generation (an important step for myelin synthesis) and for neurotransmitter production via further metabolism of acetyl-CoA in the tricarboxylic acid (TCA) cycle. However, it is not known whether reduced brain glucose transporter ty...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.04.011

    authors: Marin-Valencia I,Good LB,Ma Q,Duarte J,Bottiglieri T,Sinton CM,Heilig CW,Pascual JM

    更新日期:2012-10-01 00:00:00

  • Glial overexpression of Dube3a causes seizures and synaptic impairments in Drosophila concomitant with down regulation of the Na+/K+ pump ATPα.

    abstract::Duplication 15q syndrome (Dup15q) is an autism-associated disorder co-incident with high rates of pediatric epilepsy. Additional copies of the E3 ubiquitin ligase UBE3A are thought to cause Dup15q phenotypes, yet models overexpressing UBE3A in neurons have not recapitulated the epilepsy phenotype. We show that Drosoph...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2017.09.003

    authors: Hope KA,LeDoux MS,Reiter LT

    更新日期:2017-12-01 00:00:00

  • Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation.

    abstract::In the present study, we prepared a SCA3 animal model by generating transgenic mice expressing polyglutamine-expanded ataxin-3-Q79. Ataxin-3-Q79 was expressed in brain areas implicated in SCA3 neurodegeneration, including cerebellum, pontine nucleus and substantia nigra. Ataxin-3-Q79 transgenic mice displayed motor dy...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2008.03.011

    authors: Chou AH,Yeh TH,Ouyang P,Chen YL,Chen SY,Wang HL

    更新日期:2008-07-01 00:00:00

  • A toll-like receptor 9 antagonist reduces pain hypersensitivity and the inflammatory response in spinal cord injury.

    abstract::Toll-like receptors (TLRs) are mediators of the innate immune response to exogenous pathogens. They have also been implicated in sterile inflammation associated with systemic injury and non-infectious diseases via binding of endogenous ligands, possibly released by damaged cells. Emerging evidence indicates that some ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2012.12.012

    authors: David BT,Ratnayake A,Amarante MA,Reddy NP,Dong W,Sampath S,Heary RF,Elkabes S

    更新日期:2013-06-01 00:00:00

  • Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice.

    abstract::Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder caused by a (GCG)n trinucleotide repeat expansion in the poly(A) binding protein nuclear-1 (PABPN1) gene, which in turn leads to an expanded polyalanine tract in the protein. We generated transgenic mice expressing either the wild type or the expanded ...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2004.09.021

    authors: Dion P,Shanmugam V,Gaspar C,Messaed C,Meijer I,Toulouse A,Laganiere J,Roussel J,Rochefort D,Laganiere S,Allen C,Karpati G,Bouchard JP,Brais B,Rouleau GA

    更新日期:2005-04-01 00:00:00

  • RNAi or overexpression: alternative therapies for Spinocerebellar Ataxia Type 1.

    abstract::Spinocerebellar Ataxia Type 1 (SCA1) is an autosomal dominant late onset neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RN...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1016/j.nbd.2013.04.003

    authors: Keiser MS,Geoghegan JC,Boudreau RL,Lennox KA,Davidson BL

    更新日期:2013-08-01 00:00:00

  • Cerebrospinal fluid tissue transglutaminase as a biochemical marker for Alzheimer's disease.

    abstract::Tissue transglutaminase (tTG) is an indicator of acute cell death in vitro. An increase in tTG protein level is found in postmortem Alzheimer's disease (AD) brains as well as in Huntington's disease. No study revealed tTG in vivo so far. We investigated the concentrations of tTG in the cerebrospinal fluid (CSF) obtain...

    journal_title:Neurobiology of disease

    pub_type: 杂志文章

    doi:10.1006/nbdi.2002.0535

    authors: Bonelli RM,Aschoff A,Niederwieser G,Heuberger C,Jirikowski G

    更新日期:2002-10-01 00:00:00