Ultrastructural evidence of microglial heterogeneity in Alzheimer's disease amyloid pathology.

Abstract:

BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the deposition of extracellular fibrillar amyloid β (fΑβ) and the intracellular accumulation of neurofibrillary tangles. As AD progresses, Aβ drives a robust and prolonged inflammatory response via its recognition by microglia, the brain's immune cells. Microglial reactivity to fAβ plaques may impair their normal surveillance duties, facilitating synaptic loss and neuronal death, as well as cognitive decline in AD. METHODS:In the current study, we performed correlative light, transmission, and scanning electron microscopy to provide insights into microglial structural and functional heterogeneity. We analyzed microglial cell bodies and processes in areas containing fAβ plaques and neuronal dystrophy, dystrophy only, or appearing healthy, among the hippocampus CA1 of 14-month-old APPSwe-PS1Δe9 mice versus wild-type littermates. RESULTS:Our quantitative analysis revealed that microglial cell bodies in the AD model mice were larger and displayed ultrastructural signs of cellular stress, especially nearby plaques. Microglial cell bodies and processes were overall less phagocytic in AD model mice. However, they contained increased fibrillar materials and non-empty inclusions proximal to plaques. Microglial cell bodies and processes in AD model mice also displayed reduced association with extracellular space pockets that contained debris. In addition, microglial processes in healthy subregions of AD model mice encircled synaptic elements more often compared with plaque-associated processes. These observations in mice were qualitatively replicated in post-mortem hippocampal samples from two patients with AD (Braak stage 5). CONCLUSION:Together, our findings identify at the ultrastructural level distinct microglial transformations common to mouse and human in association with amyloid pathology.

journal_name

J Neuroinflammation

authors

El Hajj H,Savage JC,Bisht K,Parent M,Vallières L,Rivest S,Tremblay MÈ

doi

10.1186/s12974-019-1473-9

subject

Has Abstract

pub_date

2019-04-16 00:00:00

pages

87

issue

1

issn

1742-2094

pii

10.1186/s12974-019-1473-9

journal_volume

16

pub_type

杂志文章
  • CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system.

    abstract:BACKGROUND:Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Al...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0447-9

    authors: Durrant DM,Daniels BP,Pasieka T,Dorsey D,Klein RS

    更新日期:2015-12-15 00:00:00

  • Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder.

    abstract:OBJECTIVE:Converging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other de...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-10-38

    authors: Napolioni V,Ober-Reynolds B,Szelinger S,Corneveaux JJ,Pawlowski T,Ober-Reynolds S,Kirwan J,Persico AM,Melmed RD,Craig DW,Smith CJ,Huentelman MJ

    更新日期:2013-03-14 00:00:00

  • Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration.

    abstract:BACKGROUND:Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer's disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01907-0

    authors: Woollacott IOC,Toomey CE,Strand C,Courtney R,Benson BC,Rohrer JD,Lashley T

    更新日期:2020-08-10 00:00:00

  • Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.

    abstract:BACKGROUND:Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-10-122

    authors: Westhoff D,Witlox J,Koenderman L,Kalisvaart KJ,de Jonghe JF,van Stijn MF,Houdijk AP,Hoogland IC,Maclullich AM,van Westerloo DJ,van de Beek D,Eikelenboom P,van Gool WA

    更新日期:2013-10-07 00:00:00

  • Benzo(a)pyrene exposure induced neuronal loss, plaque deposition, and cognitive decline in APP/PS1 mice.

    abstract:BACKGROUND:Exposure to benzo(a)pyrene (BaP) was associated with cognitive impairments and some Alzheimer's disease (AD)-like pathological changes. However, it is largely unknown whether BaP exposure participates in the disease progression of AD. OBJECTIVES:To investigate the effect of BaP exposure on AD progression an...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01925-y

    authors: Liu D,Zhao Y,Qi Y,Gao Y,Tu D,Wang Y,Gao HM,Zhou H

    更新日期:2020-08-31 00:00:00

  • NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes.

    abstract::The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes rece...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审

    doi:10.1186/s12974-019-1498-0

    authors: Hong P,Gu RN,Li FX,Xiong XX,Liang WB,You ZJ,Zhang HF

    更新日期:2019-06-07 00:00:00

  • Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation.

    abstract:BACKGROUND:Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01870-w

    authors: Kolosowska N,Gotkiewicz M,Dhungana H,Giudice L,Giugno R,Box D,Huuskonen MT,Korhonen P,Scoyni F,Kanninen KM,Ylä-Herttuala S,Turunen TA,Turunen MP,Koistinaho J,Malm T

    更新日期:2020-06-19 00:00:00

  • Interactions between inflammatory mediators and corticosteroids regulate transcription of genes within the Kynurenine Pathway in the mouse hippocampus.

    abstract:BACKGROUND:Increased tryptophan metabolism towards the production of kynurenine via indoleamine/tryptophan-2,3-dioxygenases (DOs: Ido1, Ido2, and Tdo2) is strongly associated with the prevalence of major depressive disorder in patients and the induction of depression-like behaviors in animal models. Several studies hav...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-016-0563-1

    authors: Brooks AK,Lawson MA,Smith RA,Janda TM,Kelley KW,McCusker RH

    更新日期:2016-05-03 00:00:00

  • K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway.

    abstract:BACKGROUND:Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by gradual memory loss and neuropsychiatric symptoms. We have previously demonstrated that the 2-({3-[2-(1-cyclohexene-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanami...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-02022-w

    authors: Ham HJ,Lee YS,Yun J,Son DJ,Lee HP,Han SB,Hong JT

    更新日期:2020-11-22 00:00:00

  • Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents.

    abstract::Opioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalg...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01975-2

    authors: Doyle TM,Hutchinson MR,Braden K,Janes K,Staikopoulos V,Chen Z,Neumann WL,Spiegel S,Salvemini D

    更新日期:2020-10-22 00:00:00

  • Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood-brain barrier.

    abstract:BACKGROUND AND PURPOSE:Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) comb...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-018-1368-1

    authors: Zhao R,Jiang J,Li H,Chen M,Liu R,Sun S,Ma,Liang X,Wang S

    更新日期:2018-11-30 00:00:00

  • Acute neuroinflammation induces AIS structural plasticity in a NOX2-dependent manner.

    abstract:BACKGROUND:Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity i...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0889-3

    authors: Benusa SD,George NM,Sword BA,DeVries GH,Dupree JL

    更新日期:2017-06-08 00:00:00

  • Mannan binding lectin-associated serine protease-2 (MASP-2) critically contributes to post-ischemic brain injury independent of MASP-1.

    abstract:BACKGROUND:Complement activation via the lectin activation pathway (LP) has been identified as the key mechanism behind post-ischemic tissue inflammation causing ischemia-reperfusion injury (IRI) which can significantly impact the clinical outcome of ischemic disease. This work defines the contributions of each of the ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-016-0684-6

    authors: Orsini F,Chrysanthou E,Dudler T,Cummings WJ,Takahashi M,Fujita T,Demopulos G,De Simoni MG,Schwaeble W

    更新日期:2016-08-30 00:00:00

  • Neuroinflammation and psychiatric illness.

    abstract::Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审

    doi:10.1186/1742-2094-10-43

    authors: Najjar S,Pearlman DM,Alper K,Najjar A,Devinsky O

    更新日期:2013-04-01 00:00:00

  • Clozapine reduces infiltration into the CNS by targeting migration in experimental autoimmune encephalomyelitis.

    abstract:BACKGROUND:Atypical antipsychotic agents, such as clozapine, are used to treat schizophrenia and other psychiatric disorders by a mechanism that is believed to involve modulating the immune system. Multiple sclerosis is an immune-mediated neurological disease, and recently, clozapine was shown to reduce disease severit...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01733-4

    authors: Robichon K,Patel V,Connor B,La Flamme AC

    更新日期:2020-02-12 00:00:00

  • The blockage of the Nogo/NgR signal pathway in microglia alleviates the formation of Aβ plaques and tau phosphorylation in APP/PS1 transgenic mice.

    abstract:BACKGROUND:Alzheimer's disease (AD) is characterized by extracellular β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), and microglia-dominated neuroinflammation. The Nogo/NgR signal pathway is involved in AD pathological features, but the detailed mechanism needs further investigation. Our previous studies have ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-016-0522-x

    authors: Fang Y,Yao L,Li C,Wang J,Wang J,Chen S,Zhou XF,Liao H

    更新日期:2016-03-03 00:00:00

  • Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease.

    abstract:BACKGROUND:It has recently become apparent that neuroinflammation may play a significant role in Parkinson's disease (PD). This is also the case in animal paradigms of the disease. The potential neuroprotective action of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 (EX-4), which is protective against...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-5-19

    authors: Harkavyi A,Abuirmeileh A,Lever R,Kingsbury AE,Biggs CS,Whitton PS

    更新日期:2008-05-21 00:00:00

  • Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress.

    abstract:BACKGROUND:Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs). We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS) in stress-induced depression. METHODS:We used a depressive-like state mouse model induced by unpredictable chroni...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-9-75

    authors: Peng YL,Liu YN,Liu L,Wang X,Jiang CL,Wang YX

    更新日期:2012-07-06 00:00:00

  • T-cell reconstitution during murine acquired immunodeficiency syndrome (MAIDS) produces neuroinflammation and mortality in animals harboring opportunistic viral brain infection.

    abstract:BACKGROUND:Highly active antiretroviral therapy (HAART) restores inflammatory immune responses in AIDS patients which may unmask previous subclinical infections or paradoxically exacerbate symptoms of opportunistic infections. In resource-poor settings, 25% of patients receiving HAART may develop CNS-related immune rec...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-10-98

    authors: Mutnal MB,Schachtele SJ,Hu S,Lokensgard JR

    更新日期:2013-07-31 00:00:00

  • CCAAT/enhancer-binding protein δ (C/EBPδ) aggravates inflammation and bacterial dissemination during pneumococcal meningitis.

    abstract:BACKGROUND:The prognosis of bacterial meningitis largely depends on the severity of the inflammatory response. The transcription factor CAAT/enhancer-binding protein δ (C/EBPδ) plays a key role in the regulation of the inflammatory response during bacterial infections. Consequently, we assessed the role of C/EBPδ durin...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0309-5

    authors: Valls Serón M,Duitman J,Geldhoff M,Engelen-Lee J,Havik SR,Brouwer MC,van de Beek D,Spek CA

    更新日期:2015-05-10 00:00:00

  • Functional interleukin-17 receptor A is expressed in central nervous system glia and upregulated in experimental autoimmune encephalomyelitis.

    abstract:BACKGROUND:Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor,...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-6-14

    authors: Das Sarma J,Ciric B,Marek R,Sadhukhan S,Caruso ML,Shafagh J,Fitzgerald DC,Shindler KS,Rostami A

    更新日期:2009-04-28 00:00:00

  • Suppression of MyD88-dependent signaling alleviates neuropathic pain induced by peripheral nerve injury in the rat.

    abstract:BACKGROUND:MyD88 is the adaptor protein of MyD88-dependent signaling pathway of TLRs and IL-1 receptor and regulates innate immune response. However, it was not clear whether and how MyD88 and related signaling pathways in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) are involved in neuropathic pain. ME...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0822-9

    authors: Liu F,Wang Z,Qiu Y,Wei M,Li C,Xie Y,Shen L,Huang Y,Ma C

    更新日期:2017-03-31 00:00:00

  • Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy.

    abstract:BACKGROUND:The effectiveness of ginseng in preventing and treating various central nervous system (CNS) diseases has been widely confirmed. However, ginsenosides, the principal components of ginseng, are characterized by poor accessibility to the brain, and this pharmacokinetic-pharmacological paradox remains poorly ex...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-8-100

    authors: Kang A,Hao H,Zheng X,Liang Y,Xie Y,Xie T,Dai C,Zhao Q,Wu X,Xie L,Wang G

    更新日期:2011-08-16 00:00:00

  • High serum levels of transforming growth factor β1 are associated with increased cortical thickness in cingulate and right frontal areas in healthy subjects.

    abstract:BACKGROUND:Transforming growth factor β (TGF-β) is a cytokine having multiple functions in the central nervous system such as promoting repair mechanisms in degenerative diseases and stroke. To date, however, its neuroprotective effects in non-disease conditions have not been studied METHODS:With the aim of exploring ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-9-42

    authors: Piras F,Salani F,Bossù P,Caltagirone C,Spalletta G

    更新日期:2012-02-28 00:00:00

  • Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling.

    abstract:BACKGROUND:Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson's disease (PD). The pathogenesis of this type of neurological disorders often involv...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-11-47

    authors: Liu RP,Zou M,Wang JY,Zhu JJ,Lai JM,Zhou LL,Chen SF,Zhang X,Zhu JH

    更新日期:2014-03-12 00:00:00

  • Quinolinic acid toxicity on oligodendroglial cells: relevance for multiple sclerosis and therapeutic strategies.

    abstract::The excitotoxin quinolinic acid, a by-product of the kynurenine pathway, is known to be involved in several neurological diseases including multiple sclerosis (MS). Quinolinic acid levels are elevated in experimental autoimmune encephalomyelitis rodents, the widely used animal model of MS. Our group has also found pat...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-014-0204-5

    authors: Sundaram G,Brew BJ,Jones SP,Adams S,Lim CK,Guillemin GJ

    更新日期:2014-12-13 00:00:00

  • Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid.

    abstract:BACKGROUND:Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospin...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0450-1

    authors: Wuhrer M,Selman MH,McDonnell LA,Kümpfel T,Derfuss T,Khademi M,Olsson T,Hohlfeld R,Meinl E,Krumbholz M

    更新日期:2015-12-18 00:00:00

  • Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide.

    abstract::BACKGROUND: Roles for excitotoxicity and inflammation in Alzheimer's disease have been hypothesized. Proinflammatory stimuli, including amyloid beta-peptide (Abeta), elicit a release of glutamate from microglia. We tested the possibility that a coagonist at the NMDA class of glutamate receptors, D-serine, could respon...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-1-2

    authors: Wu SZ,Bodles AM,Porter MM,Griffin WS,Basile AS,Barger SW

    更新日期:2004-04-20 00:00:00

  • Impact of combined sodium chloride and saturated long-chain fatty acid challenge on the differentiation of T helper cells in neuroinflammation.

    abstract:BACKGROUND:There has been a marked increase in the incidence of autoimmune diseases like multiple sclerosis (MS) in the last decades which is most likely driven by a change in environmental factors. Here, growing evidence suggests that ingredients of a Western diet like high intake of sodium chloride (NaCl) or saturate...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0954-y

    authors: Hammer A,Schliep A,Jörg S,Haghikia A,Gold R,Kleinewietfeld M,Müller DN,Linker RA

    更新日期:2017-09-12 00:00:00

  • Alterations of peripheral nerve excitability in an experimental autoimmune encephalomyelitis mouse model for multiple sclerosis.

    abstract:BACKGROUND:Experimental autoimmune encephalomyelitis (EAE) is the most commonly used and clinically relevant murine model for human multiple sclerosis (MS), a demyelinating autoimmune disease characterized by mononuclear cell infiltration into the central nervous system (CNS). The aim of the present study was to apprai...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01936-9

    authors: Teixeira NB,Picolo G,Giardini AC,Boumezbeur F,Pottier G,Kuhnast B,Servent D,Benoit E

    更新日期:2020-09-07 00:00:00