Chronic brain inflammation leads to a decline in hippocampal NMDA-R1 receptors

BackgroundNeuroinflammation plays a prominent role in the progression of Alzheimer's disease and may be responsible for degeneration in vulnerable regions such as the hippocampus. Neuroinflammation is associated with elevated levels of extracellular glutamate and potentially an enhanced stimulation of glutamate N-methyl-D-aspartate receptors. This suggests that neurons that express these glutamate receptors might be at increased risk of degeneration in the presence of chronic neuroinflammation.MethodsWe have characterized a novel model of chronic brain inflammation using a slow infusion of lipopolysaccharide into the 4th ventricle of rats. This model reproduces many of the behavioral, electrophysiological, neurochemical and neuropathological changes associated with Alzheimer's disease.ResultsThe current study demonstrated that chronic neuroinflammation is associated with the loss of N-methyl-D-aspartate receptors, as determined both qualitatively by immunohistochemistry and quantitatively by in vitro binding studies using [3H]MK-801, within the hippocampus and entorhinal cortex.ConclusionThe gradual loss of function of this critical receptor within the temporal lobe region may contribute to some of the cognitive deficits observed in patients with Alzheimer's disease.

• Publication year

  2004

• Venue

  Journal of Neuroinflammation

• Publication date

  2004-07-07

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1742-2094-1-12PMID 15285803PMCID 500869
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The neuropharmacological basis for the use of memantine in the treatment of Alzheimer's disease.

  2006cited by this paper
• Inflammation in Alzheimer’s disease

  2006cited by this paper
• Sulindac improves memory and increases NMDA receptor subunits in aged Fischer 344 rats.

  2004cited by this paper
• Neuropathological stageing of Alzheimer-related changes

  2004cited by this paper
• Chronic Intracerebral LPS as a Model of Neuroinflammation

  2003cited by this paper
• The toxicity of tumor necrosis factor-α upon cholinergic neurons within the nucleus basalis and the role of norepinephrine in the regulation of inflammation: implications for alzheimer's disease

  2003cited by this paper
• Neuroinflammation : mechanisms and management

  2003cited by this paper
• Interleukin-1β Enhances NMDA Receptor-Mediated Intracellular Calcium Increase through Activation of the Src Family of Kinases

  2003cited by this paper
• Glutamate receptor function in learning and memory.

  2003cited by this paper
• N-methyl-D-aspartate receptor subunit NR2A and NR2B messenger RNA levels are altered in the hippocampus and entorhinal cortex in Alzheimer's disease.

  2002cited by this paper
• Alterations of NMDAR1 and NMDAR2A/B immunoreactivity in the hippocampus after perforant pathway lesion

  2002cited by this paper
• Region‐selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

  2002cited by this paper
• Chronic brain inflammation results in cell loss in the entorhinal cortex and impaired LTP in perforant path-granule cell synapses.

  2002influential reference
• Acute neuroinflammation exacerbates excitotoxicity in rat hippocampus in vivo.

  2002cited by this paper
• Inflammation in Alzheimer’s Disease

  2001cited by this paper
• In-vivo measurement of activated microglia in dementia.

  2001cited by this paper
• CXCR4-activated astrocyte glutamate release via TNFα: amplification by microglia triggers neurotoxicity

  2001cited by this paper
• Neuroprotective effects of extracellular glutamate are absent in hippocampal organotypic cultures treated with the amyloid peptide Aβ25–35

  2001cited by this paper
• Inflammatory Neurodegeneration Mediated by Nitric Oxide from Activated Glia-Inhibiting Neuronal Respiration, Causing Glutamate Release and Excitotoxicity

  2001cited by this paper
• Neuroprotective effects of extracellular glutamate are absent in hippocampal organotypic cultures treated with the amyloid peptide Abeta(25-35).

  2001cited by this paper
• LPS‐induced neuroinflammatory effects do not recover with time

  2000cited by this paper
• Inflammation and Alzheimer's disease.

  2000cited by this paper
• Behavioral and ultrastructural changes induced by chronic neuroinflammation in young rats.

  2000cited by this paper
• Mechanisms to prevent the toxicity of chronic neuroinflammation on forebrain cholinergic neurons.

  2000cited by this paper
• Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat.

  2000cited by this paper
• Quantitative volumetric analyses of brain magnetic resonance imaging from rat with chronic neuroinflammation.

  2000cited by this paper
• The effects of a novel NSAID on chronic neuroinflammation are age dependent.

  1999cited by this paper
• Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease.

  1998influential reference
• The importance of inflammatory mechanisms in Alzheimer disease.

  1998cited by this paper
• Prostaglandins stimulate calcium-dependent glutamate release in astrocytes

  1998cited by this paper
• Altered glutamatergic transmission in neurological disorders: from high extracellular glutamate to excessive synaptic efficacy.

  1997cited by this paper
• Alzheimer’s Disease: In Vivo Detection of Differential Vulnerability of Brain Regions

  1997cited by this paper
• Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease

  1996cited by this paper
• Induction of Prostanoid Biosynthesis by Bacterial Lipopolysaccharide and Isoproterenol in Rat Microglial Cultures

  1995cited by this paper
• Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.

  1995cited by this paper
• Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide.

  1994cited by this paper
• Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity.

  1993cited by this paper
• Inhibition of Glutamate Uptake with l‐trans‐Pyrrolidine‐2,4‐Dicarboxylate Potentiates Glutamate Toxicity in Primary Hippocampal Cultures

  1993cited by this paper
• Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes

  1992cited by this paper
• Alternative excitotoxic hypotheses

  1992cited by this paper
• Interleukin-1 beta increases prostaglandin E2 in rat astrocyte cultures: modulatory effect of neuropeptides.

  1989cited by this paper
• Protein measurement with the Folin phenol reagent.

  1951cited by this paper

• Effects of Oral Administration of the Probiotic Lactobacillus rhamnosus GG on the Proteomic Profiles of Cerebrospinal Fluid and Immunoregulatory Signaling in the Hippocampus of Adult Male Rats

  2025cites this paper
• Persistent neuroinflammation and functional deficits in a murine model of decompression sickness.

  2024cites this paper
• Atherosclerosis and Hippocampal Volumes in Older Adults: The Role of Age and Blood Pressure

  2024cites this paper
• Alzheimer’s Disease-like Pathological Features in the Dorsal Hippocampus of Wild-Type Rats Subjected to Methionine-Diet-Evoked Mild Hyperhomocysteinaemia

  2023cites this paper
• Metabolomic, lipidomic and proteomic characterisation of lipopolysaccharide-induced inflammation mouse model.

  2022cites this paper
• Is Periodontitis Associated with Age-Related Cognitive Impairment? The Systematic Review, Confounders Assessment and Meta-Analysis of Clinical Studies

  2022cites this paper
• Granulocyte Colony-Stimulating Factor Improved Core Symptoms of Autism Spectrum Disorder via Modulating Glutamatergic Receptors in the Prefrontal Cortex and Hippocampus of Rat Brains.

  2022cites this paper
• Hizikia fusiforme functional oil (HFFO) prevents neuroinflammation and memory deficits evoked by lipopolysaccharide/aluminum trichloride in zebrafish

  2022cites this paper
• Transient neuroinflammation following surgery contributes to long-lasting cognitive decline in elderly rats via dysfunction of synaptic NMDA receptor

  2022cites this paper
• Anti-Inflammatory Activity of N-Docosahexaenoylethanolamine and N-Eicosapentaenoylethanolamine in a Mouse Model of Lipopolysaccharide-Induced Neuroinflammation

  2021cites this paper
• Curcumin modulates long term potentiation in lipopolysaccharide-treated rats

  2020cites this paper
• Peripheral inflammation exacerbates α‐synuclein toxicity and neuropathology in Parkinson's models

  2020cites this paper
• N-Docosahexanoylethanolamine Reduces Microglial Activation and Improves Hippocampal Plasticity in a Murine Model of Neuroinflammation

  2020influential citation
• Calcium Signaling During Brain Aging and Its Influence on the Hippocampal Synaptic Plasticity.

  2020cites this paper
• Psychobiotics: A Novel Approach to the Treatment ofMental Diseases

  2019cites this paper
• Noxious Iron–Calcium Connections in Neurodegeneration

  2019cites this paper
• Stearoylethanolamide interferes with retrograde endocannabinoid signalling and supports the blood-brain barrier integrity under acute systemic inflammation.

  2019cites this paper
• Trans-cinnamaldehyde Improves Neuroinflammation-mediated NMDA Receptor Dysfunction and Memory Deficits through Blocking NF-κB Pathway in Presenilin1/2 Conditional Double Knockout Mice.

  2019cites this paper
• Unique Contribution of Haptoglobin and Haptoglobin Genotype in Aneurysmal Subarachnoid Hemorrhage

  2018cites this paper
• Sleep-Aids Derived from Natural Products

  2018cites this paper
• AN OVERVIEW OF INSOMNIA

  2018cites this paper
• Minocycline diminishes the rotenone induced neurotoxicity and glial activation via suppression of apoptosis, nitrite levels and oxidative stress

  2018cites this paper
• IL1R2, CCR2, and CXCR4 May Form Heteroreceptor Complexes with NMDAR and D2R: Relevance for Schizophrenia

  2017cites this paper
• Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat.

  2016cites this paper
• Behavioral and monoamine perturbations in adult male mice with chronic inflammation induced by repeated peripheral lipopolysaccharide administration.

  2016cites this paper
• Trans-cinnamaldehyde improves memory impairment by blocking microglial activation through the destabilization of iNOS mRNA in mice challenged with lipopolysaccharide.

  2016cites this paper
• Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

  2016cites this paper
• Cardiotonic Steroids as Modulators of Neuroinflammation

  2016cites this paper
• Initiating Mechanisms of Surgery-induced Memory Decline: The Role of HMGB1.

  2016cites this paper
• Spermine reverses lipopolysaccharide-induced memory deficit in mice

  2015cites this paper
• Methemoglobin Is an Endogenous Toll-Like Receptor 4 Ligand—Relevance to Subarachnoid Hemorrhage

  2015cites this paper
• Erratum to: Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains

  2015cites this paper
• NMDA Receptor Function During Senescence: Implication on Cognitive Performance

  2015cites this paper
• Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains

  2015cites this paper
• Erratum to: Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains

  2015cites this paper
• An Examination of the Long-lasting Effects of Lipopolysaccharide-induced Sepsis on Cognitive and Affective Behaviour in Mice

  2014cites this paper
• Chronic brain inflammation causes a reduction in GluN2A and GluN2B subunits of NMDA receptors and an increase in the phosphorylation of mitogen-activated protein kinases in the hippocampus

  2014influential citation
• Inflammatory Pathways of Radiation‐Induced Tissue Injury

  2014cites this paper
• Age and duration of inflammatory environment differentially affect the neuroimmune response and catecholaminergic neurons in the midbrain and brainstem.

  2014cites this paper
• Bacterial lipopolysaccharide induces a dose-dependent activation of neuroglia and loss of basal forebrain cholinergic cells in the rat brain.

  2014cites this paper
• Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus.

  2013cites this paper
• Time-Dependent Compensatory Responses to Chronic Neuroinflammation in Hippocampus and Brainstem: The Potential Role of Glutamate Neurotransmission

  2013cites this paper
• Examining the Acute and Chronic Effects of Sepsis on the Circadian Clock in the Mouse

  2013cites this paper
• Peripheral administration of D-cycloserine rescues memory consolidation following bacterial endotoxin exposure.

  2013cites this paper
• A pro-inflammatory agent, Lipopolysaccharide, can mimic the effects ofaging on spatial reference memory

  2013cites this paper
• Patterns of histone acetylation as targets for novel therapeutic approaches in neurological diseases

  2013cites this paper
• Riluzole Partially Rescues Age-Associated, but not LPS-Induced, Loss of Glutamate Transporters and Spatial Memory

  2013cites this paper
• Tumor necrosis factor-α synthesis inhibitor 3,6′-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer’s disease

  2012cites this paper
• Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors

  2012cites this paper
• TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

  2012cites this paper
• Lipopolysaccharide induces paired immunoglobulin-like receptor B (PirB) expression, synaptic alteration, and learning-memory deficit in rats.

  2012cites this paper
• The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus

  2012cites this paper
• Natural polyphenols against neurodegenerative disorders: potentials and pitfalls.

  2012cites this paper
• Telomere Shortening and Alzheimer’s Disease

  2012cites this paper
• Tumor necrosis factor-alpha synthesis inhibitor 3,6' -dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer's disease

  2012cites this paper
• Neuroréanimation et sujets âgés

  2012cites this paper
• Acetate supplementation attenuates lipopolysaccharide‐induced neuroinflammation

  2011cites this paper
• Effects of Scutellaria baicalensis on chronic cerebral hypoperfusion-induced memory impairments and chronic lipopolysaccharide infusion-induced memory impairments.

  2011cites this paper
• Central effects of a local inflammation in three commonly used mouse strains with a different anxious phenotype.

  2011cites this paper
• Involvement of interleukin‐1 in lipopolysaccaride‐induced microglial activation and learning and memory deficits

  2011cites this paper
• Neuroinflammation and the plasticity-related immediate-early gene Arc.

  2011cites this paper
• Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

  2011cites this paper
• Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice.

  2010cites this paper
• Rat brain docosahexaenoic acid metabolism is not altered by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide.

  2010cites this paper
• Anti-neuroinflammatory activity of nobiletin on suppression of microglial activation.

  2010cites this paper
• Functional Aspects of Redox Control During Neuroinflammation

  2010cites this paper
• Impairment of long-term depression induced by chronic brain inflammation in rats.

  2009cites this paper
• Chronic brain inflammation impairs two forms of long-term potentiation in the rat hippocampal CA1 area.

  2009cites this paper
• Critical appraisal of the long-term impact of memantine in treatment of moderate to severe Alzheimer’s disease

  2009cites this paper
• Stimulation of Toll-Like Receptor 9 by Chronic Intraventricular Unmethylated Cytosine-Guanine DNA Infusion Causes Neuroinflammation and Impaired Spatial Memory

  2009cites this paper
• Dexibuprofen (S(+)-isomer ibuprofen) reduces microglial activation and impairments of spatial working memory induced by chronic lipopolysaccharide infusion.

  2008influential citation
• Construction and implantation of a microinfusion system for sustained delivery of neuroactive agents.

  2008cites this paper
• Construction and implantation of a microinfusion system for sustained delivery of neuroactive agents.

  2008cites this paper
• Macelignan attenuates LPS-induced inflammation and reduces LPS-induced spatial learning impairments in rats.

  2008cites this paper
• Chronic NMDA Administration Increases Neuroinflammatory Markers in Rat Frontal Cortex: Cross-Talk Between Excitotoxicity and Neuroinflammation

  2008cites this paper
• Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent model of chronic brain inflammation.

  2007cites this paper
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  2007cites this paper
• Polymodal Regulation of NMDA Receptor-Channels

  2007cites this paper
• Neurodegenerative diseases and memory

  2007cites this paper
• Liposome reconstitution and modulation of recombinant N-methyl-d-aspartate receptor channels by membrane stretch

  2007cites this paper
• Molecular and cellular characterization of the age‐related neuroinflammatory processes occurring in normal rat hippocampus: potential relation with the loss of somatostatin GABAergic neurons

  2007cites this paper
• Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior.

  2007cites this paper
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  2006cites this paper
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  2006cites this paper
• Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat.

  2006cites this paper
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  2005influential citation
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  2005cites this paper
• Chemokine receptor 5 antagonist D-Ala-peptide T-amide reduces microglia and astrocyte activation within the hippocampus in a neuroinflammatory rat model of Alzheimer's disease.

  2005cites this paper
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  year unknowncites this paper
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  year unknowncites this paper