HIV-associated synaptic degeneration

Human immunodeficiency virus (HIV) infection induces neuronal injuries, with almost 50% of infected individuals developing HIV-associated neurocognitive disorders (HAND). Although highly activate antiretroviral therapy (HAART) has significantly reduced the incidence of severe dementia, the overall prevalence of HAND remains high. Synaptic degeneration is emerging as one of the most relevant neuropathologies associate with HAND. Previous studies have reported critical roles of viral proteins and inflammatory responses in this pathogenesis. Infected cells, including macrophages, microglia and astrocytes, may release viral proteins and other neurotoxins to stimulate neurons and cause excessive calcium influx, overproduction of free radicals and disruption of neurotransmitter hemostasis. The dysregulation of neural circuits likely leads to synaptic damage and loss. Identification of the specific mechanism of the synaptic degeneration may facilitate the development of effective therapeutic approaches to treat HAND.

• Publication year

  2017

• Venue

  Molecular Brain

• Publication date

  2017-08-29

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s13041-017-0321-zPMID 28851400PMCID 5576336
• 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.

• Effects of Morphine on Behavioral Task Performance in SIV-Infected Rhesus Macaques

  2016cited by this paper
• HIV encephalopathy: glial activation and hippocampal neuronal apoptosis, but limited neural repair

  2016cited by this paper
• HIV-associated neurocognitive disorder — pathogenesis and prospects for treatment

  2016cited by this paper
• Complement and microglia mediate early synapse loss in Alzheimer mouse models

  2016cited by this paper
• A complement–microglial axis drives synapse loss during virus-induced memory impairment

  2016cited by this paper
• Microglial phagocytosis and activation underlying photoreceptor degeneration is regulated by CX3CL1‐CX3CR1 signaling in a mouse model of retinitis pigmentosa

  2016cited by this paper
• Novel allele-dependent role for APOE in controlling the rate of synapse pruning by astrocytes

  2016cited by this paper
• The complement system, neuronal injury, and cognitive function in horizontally-acquired HIV-infected youth

  2016cited by this paper
• The complement system, neuronal injury, and cognitive function in horizontally-acquired HIV-infected youth

  2016cited by this paper
• HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors

  2016cited by this paper
• Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET

  2016cited by this paper
• Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases

  2015cited by this paper
• Magnetic Resonance Imaging Study of a Simian/Human Immunodeficiency Virus-Infected Chinese Rhesus Macaque with HIV-Associated Dementia

  2015cited by this paper
• Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice

  2015cited by this paper
• Astrocytes Control Synapse Formation, Function, and Elimination.

  2015cited by this paper
• Do glia drive synaptic and cognitive impairment in disease?

  2015cited by this paper
• Studies of retroviral infection in humanized mice.

  2015cited by this paper
• Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity

  2014cited by this paper
• Associations between brain microstructures, metabolites, and cognitive deficits during chronic HIV-1 infection of humanized mice

  2014cited by this paper
• Glutamate metabolism and HIV-associated neurocognitive disorders

  2014cited by this paper
• Giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques

  2014influential reference
• Fine-tuning the central nervous system: microglial modelling of cells and synapses

  2014cited by this paper
• Microglial phagocytosis of live neurons

  2014cited by this paper
• Complement and HIV-I infection/HIV-associated neurocognitive disorders

  2014cited by this paper
• CCR5 Knockout Prevents Neuronal Injury and Behavioral Impairment Induced in a Transgenic Mouse Model by a CXCR4-Using HIV-1 Glycoprotein 120

  2014cited by this paper
• Astrocyte Dysfunctions and HIV-1 Neurotoxicity

  2013cited by this paper
• Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.

  2013cited by this paper
• 14-3-3 Protein in CSF reflects SIV-mediated pre-synaptic damage.

  2013cited by this paper
• Effect of morphine and SIV on dendritic cell trafficking into the central nervous system of rhesus macaques

  2013cited by this paper
• Targeting the Glutamatergic System for the Treatment of HIV-Associated Neurocognitive Disorders

  2013cited by this paper
• Mice Transgenic for CD4-Specific Human CD4, CCR5 and Cyclin T1 Expression: A New Model for Investigating HIV-1 Transmission and Treatment Efficacy

  2013cited by this paper
• Synaptic dysfunction in the hippocampus accompanies learning and memory deficits in human immunodeficiency virus type-1 Tat transgenic mice.

  2013cited by this paper
• Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory.

  2013cited by this paper
• Review: Activation patterns of microglia and their identification in the human brain

  2013cited by this paper
• Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus

  2013cited by this paper
• Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

  2013cited by this paper
• Cytokines in CSF correlate with HIV-associated neurocognitive disorders in the post-HAART era in China

  2013cited by this paper
• Expression of HIV-Tat protein is associated with learning and memory deficits in the mouse.

  2012cited by this paper
• Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.

  2012cited by this paper
• HIV-1 gp120 induces antioxidant response element-mediated expression in primary astrocytes: role in HIV associated neurocognitive disorder.

  2012cited by this paper
• Mitochondrial Glutaminase Release Contributes to Glutamate-Mediated Neurotoxicity during Human Immunodeficiency Virus-1 Infection

  2012cited by this paper
• Animal models for HIV/AIDS research

  2012cited by this paper
• Acute encephalitis as initial presentation of primary HIV infection

  2012cited by this paper
• Neuronal toxicity in HIV CNS disease.

  2012cited by this paper
• The chemokine CXCL12 and the HIV‐1 envelope protein gp120 regulate spontaneous activity of Cajal–Retzius cells in opposite directions

  2012cited by this paper
• HIV-1 Tat-induced microglial activation and neuronal damage is inhibited via CD45 modulation: A potential new treatment target for HAND.

  2012cited by this paper
• Subtype selective NMDA receptor antagonists induce recovery of synapses lost following exposure to HIV‐1 Tat

  2012cited by this paper
• Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV

  2011cited by this paper
• Morphine Potentiates Neuropathogenesis of SIV Infection in Rhesus Macaques

  2011cited by this paper
• Chemokines in cerebrospinal fluid correlate with cerebral metabolite patterns in HIV-infected individuals

  2011cited by this paper
• Activation of Cannabinoid Type 2 Receptors Inhibits HIV-1 Envelope Glycoprotein gp120-Induced Synapse Loss

  2011cited by this paper
• The Human Immunodeficiency Virus Coat Protein gp120 Promotes Forward Trafficking and Surface Clustering of NMDA Receptors in Membrane Microdomains

  2011influential reference
• CX₃CR1 deficiency exacerbates neuronal loss and impairs early regenerative responses in the target-ablated olfactory epithelium.

  2011cited by this paper
• Rescue of adult hippocampal neurogenesis in a mouse model of HIV neurologic disease.

  2011cited by this paper
• Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

  2011cited by this paper
• Breaking down the barrier: the effects of HIV-1 on the blood-brain barrier.

  2011cited by this paper
• HIV-1 gp120 Induces Expression of IL-6 through a Nuclear Factor-Kappa B-Dependent Mechanism: Suppression by gp120 Specific Small Interfering RNA

  2011influential reference
• HIV-1 envelope protein gp120 up regulates CCL5 production in astrocytes which can be circumvented by inhibitors of NF-κB pathway.

  2011cited by this paper
• Fractalkine/CX3CL1 protects striatal neurons from synergistic morphine and HIV-1 Tat-induced dendritic losses and death

  2011cited by this paper
• Loss of Neuronal Integrity during Progressive HIV-1 Infection of Humanized Mice

  2011cited by this paper
• Human Immunodeficiency Virus Infection of Human Astrocytes Disrupts Blood–Brain Barrier Integrity by a Gap Junction-Dependent Mechanism

  2011cited by this paper
• Virus-host interaction in the simian immunodeficiency virus-infected brain

  2011cited by this paper
• The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART.

  2010cited by this paper
• Methamphetamine increases brain viral load and activates natural killer cells in simian immunodeficiency virus-infected monkeys.

  2010cited by this paper
• The good and evil of complement activation in HIV-1 infection

  2010cited by this paper
• Interactive comorbidity between opioid drug abuse and HIV-1 Tat: chronic exposure augments spine loss and sublethal dendritic pathology in striatal neurons.

  2010cited by this paper
• A Novel CCR5 Mutation Common in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-Null Natural Hosts and Efficient Alternative Coreceptor Use In Vivo

  2010cited by this paper
• Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease

  2010cited by this paper
• Fractalkine Attenuates Excito-neurotoxicity via Microglial Clearance of Damaged Neurons and Antioxidant Enzyme Heme Oxygenase-1 Expression*

  2010cited by this paper
• Immunopathology and Infectious Diseases Links between Progressive HIV-1 Infection of Humanized Mice and Viral Neuropathogenesis

  2010cited by this paper
• Simian immunodeficiency virus-infected macaques treated with highly active antiretroviral therapy have reduced central nervous system viral replication and inflammation but persistence of viral DNA.

  2010cited by this paper
• Activation of p38 MAPK Is Required in Monocytic and Neuronal Cells for HIV Glycoprotein 120-Induced Neurotoxicity

  2010cited by this paper
• CXCL12 inhibits expression of the NMDA receptor's NR2B subunit through a histone deacetylase-dependent pathway contributing to neuronal survival

  2010cited by this paper
• Early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys

  2009cited by this paper
• Further characterization of the spatial learning deficit in the human immunodeficiency virus-1 transgenic rat

  2009cited by this paper
• A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder.

  2009cited by this paper
• HIV Infection and the Central Nervous System: A Primer

  2009cited by this paper
• Morphine enhances Tat-induced activation in murine microglia

  2009cited by this paper
• Monocyte Chemoattractant Protein-1 (MCP-1): An Overview

  2009cited by this paper
• Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

  2009cited by this paper
• Tissue-Specific Sequence Alterations in the Human Immunodeficiency Virus Type 1 Envelope Favoring CCR5 Usage Contribute to Persistence of Dual-Tropic Virus in the Brain

  2009cited by this paper
• NMDA Receptor Activation by HIV-Tat Protein Is Clade Dependent

  2008cited by this paper
• HIV and antiretroviral therapy in the brain: neuronal injury and repair

  2008cited by this paper
• Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration

  2008cited by this paper
• Increased In Vivo Activation of Microglia and Astrocytes in the Brains of Mice Transgenic for an Infectious R5 Human Immunodeficiency Virus Type 1 Provirus and for CD4-Specific Expression of Human Cyclin T1 in Response to Stimulation by Lipopolysaccharides

  2008cited by this paper
• Morphine causes rapid increases in glial activation and neuronal injury in the striatum of inducible HIV‐1 tat transgenic mice

  2008cited by this paper
• HIV-1 Clade-Specific Differences in the Induction of Neuropathogenesis

  2008cited by this paper
• The chemokine CXCL12 promotes survival of postmitotic neurons by regulating Rb protein

  2008cited by this paper
• Human Immunodeficiency Virus Protein Tat Induces Synapse Loss via a Reversible Process That Is Distinct from Cell Death

  2008cited by this paper
• Cerebrospinal fluid markers in central nervous system HIV infection and AIDS dementia complex.

  2007cited by this paper
• Updated research nosology for HIV-associated neurocognitive disorders

  2007cited by this paper
• Spatial Learning and Memory in HIV-1 Transgenic Rats

  2007cited by this paper
• HIV-susceptible transgenic rats allow rapid preclinical testing of antiviral compounds targeting virus entry or reverse transcription

  2007cited by this paper
• The classical complement cascade mediates CNS synapse elimination.

  2007cited by this paper
• An evaluation of neurocognitive status and markers of immune activation as predictors of time to death in advanced HIV infection.

  2007cited by this paper
• Gap Junctions Mediate Human Immunodeficiency Virus-Bystander Killing in Astrocytes

  2007cited by this paper
• Highly active antiretroviral therapy of cognitive dysfunction and neuronal abnormalities in SCID mice with HIV encephalitis.

  2007cited by this paper
• Associative and predictive biomarkers of dementia in HIV-1–infected patients

  2007cited by this paper
• HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest.

  2007cited by this paper
• Brain‐Derived Neurotrophic Factor Prevents Human Immunodeficiency Virus Type 1 Protein gp120 Neurotoxicity in the Rat Nigrostriatal System

  2007cited by this paper

• EcoHIV Infection Disrupts Dopamine and Serotonin Transporter Function, Altering Release Dynamics in C57BL/6J Mice

  2026cites this paper
• Viral modulation of synaptic pruning: implications for neuropathology and brain function

  2026cites this paper
• HIF‐1 Targeting Intervention Renders Protection From Alzheimer's‐Like Pathology in a Humanized Mice Model of HIV Infection

  2025cites this paper
• CSF Beta-Synuclein, SNAP-25, and Neurogranin in Infectious and Autoimmune Inflammatory Neurologic Diseases

  2025cites this paper
• Multifaceted Role of Nef in HIV-Associated Neurocognitive Disorder: Histopathological Alterations and Underlying Mechanisms

  2025cites this paper
• Brain levels of the neurotransmitter γ-aminobutyric acid are reduced in people with HIV-related neuropathic pain.

  2025cites this paper
• Chemogenetic activation of medial prefrontal cortex projections to the nucleus accumbens shell suppresses cocaine-primed reinstatement in EcoHIV infected mice.

  2025cites this paper
• Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain Regions

  2025cites this paper
• Chemogenetic Activation of Medial Prefrontal Cortex Projections to the Nucleus Accumbens Shell Suppresses Cocaine-Primed Reinstatement in EcoHIV Infected Mice

  2025cites this paper
• Decoding HIV-associated neurocognitive disorders: a new perspective from multimodal connectomics

  2025cites this paper
• Identification of a reactive astrocyte subpopulation during HIV-associated pain pathogenesis in mouse models

  2025cites this paper
• High Levels of Monocyte Chemoattractant Protein-1 Plasma Are A Risk Factor for Neurocognitive Disorders in Human Immunodeficiency Virus Infection with Antiretroviral Therapy

  2024cites this paper
• SARS-CoV-2 Nsp7 plays a role in cognitive dysfunction by impairing synaptic plasticity

  2024cites this paper
• Modulation of tenofovir by probenecid: Impact on drug, interleukin-1β, and dopamine concentration in the prefrontal cortex and cerebellum.

  2024cites this paper
• Is There such a Thing as Post-Viral Depression?: Implications for Precision Medicine

  2024cites this paper
• Levetiracetam Prevents Neurophysiological Changes and Preserves Cognitive Function in the Human Immunodeficiency Virus (HIV)-1 Transactivator of Transcription Transgenic Mouse Model of HIV-Associated Neurocognitive Disorder

  2024cites this paper
• Short‐term exposure to HIV Tat induces glial activation and changes in perineuronal nets

  2024cites this paper
• Discovery of long non-coding RNAs in naïve CD4+ T cells in response to initiating antiretroviral therapy at acute or chronic phase of HIV-1 infection

  2024cites this paper
• Unravelling the triad of neuroinvasion, neurodissemination, and neuroinflammation of human immunodeficiency virus type 1 in the central nervous system

  2024cites this paper
• Interferon-β deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.

  2024cites this paper
• Human microglial models to study host-virus interactions.

  2023cites this paper
• HIV-1 Tat commandeers nuclear export of Rev-viral RNA complex by controlling hnRNPA2-mediated splicing

  2023cites this paper
• Pathogenesis and outcome of VA1 astrovirus infection in the human brain are defined by disruption of neural functions and imbalanced host immune responses

  2023cites this paper
• Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain

  2023cites this paper
• HIV-1 envelope protein gp120 modulation of glutamate effects on cortical neuronal synapses: implications for HIV-1-associated neuropathogenesis.

  2023cites this paper
• HIV Tat-mediated altered oligodendrocyte maturation involves autophagy-lysosomal dysfunction

  2023cites this paper
• Role of Dysregulated Autophagy in HIV Tat, Cocaine, and cART Mediated NLRP3 Activation in Microglia

  2023influential citation
• 17⍺-Estradiol Protects against HIV-1 Tat-Induced Endolysosome Dysfunction and Dendritic Impairments in Neurons

  2023cites this paper
• Targeting C–C Chemokine Receptor 5: Key to Opening the Neurorehabilitation Window After Ischemic Stroke

  2022cites this paper
• Inhibitory Neurotransmission Is Sex-Dependently Affected by Tat Expression in Transgenic Mice and Suppressed by the Fatty Acid Amide Hydrolase Enzyme Inhibitor PF3845 via Cannabinoid Type-1 Receptor Mechanisms

  2022cites this paper
• Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

  2022cites this paper
• HIV-1 Tat induced microglial EVs leads to neuronal synaptodendritic injury: microglia-neuron cross-talk in NeuroHIV

  2022cites this paper
• Aberrant Synaptic Pruning in CNS Diseases: A Critical Player in HIV-Associated Neurological Dysfunction?

  2022cites this paper
• The role of CCR5 in HIV-associated neurocognitive disorders

  2022cites this paper
• A novel subtype of reactive astrocytes critical for HIV associated pain pathogenesis

  2022cites this paper
• Imbalanced immune response and dysregulation of neural functions underline fatal opportunistic encephalitis caused by astrovirus

  2022cites this paper
• Brief Report: Polymorphisms in CAMKK2 may Influence Domain-Specific Neurocognitive Function in HIV+ Indonesians Receiving ART

  2021cites this paper
• Amyloidogenic, neuroinflammatory and memory dysfunction effects of HIV-1 gp120

  2021cites this paper
• Brain Volumetric Alterations in Preclinical HIV-Associated Neurocognitive Disorder Using Automatic Brain Quantification and Segmentation Tool

  2021cites this paper
• HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments

  2021cites this paper
• Neurocognitive outcomes in indonesians living with HIV are influenced by polymorphisms in the gene encoding purinergic P2X receptor 7

  2021cites this paper
• Possible Mechanisms of HIV Neuro-Infection in Alcohol Use: Interplay of Oxidative Stress, Inflammation, and Energy Interruption.

  2021cites this paper
• Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders

  2021cites this paper
• The neuropsychiatric manifestations of COVID-19: Interactions with psychiatric illness and pharmacological treatment

  2021cites this paper
• Retroviral infection of human neurospheres and use of stem Cell EVs to repair cellular damage

  2021cites this paper
• CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice

  2021influential citation
• Osteopontin and Integrin Mediated Modulation of Post-Synapses in HIV Envelope Glycoprotein Exposed Hippocampal Neurons

  2020cites this paper
• Wnt/β-catenin signaling regulates brain-derived neurotrophic factor release from spinal microglia to mediate HIV1 gp120-induced neuropathic pain

  2020cites this paper
• Cerebral toxoplasmosis in HIV-infected patients over 2015–2018 (a case study of Russia)

  2020cites this paper
• Successful Utilization of Levodopa in HIV-Induced Parkinsonism

  2020cites this paper
• Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

  2020cites this paper
• Expression of HIV-1 Intron-Containing RNA in Microglia Induces Inflammatory Responses

  2020cites this paper
• Insight into the roles of CCR5 in learning and memory in normal and disordered states.

  2020cites this paper
• Opioid-Mediated HIV-1 Immunopathogenesis

  2020cites this paper
• The delicate balance between neurotoxicity and neuroprotection in the context of HIV‐1 infection

  2020cites this paper
• N-Acetylcysteine Reverses Antiretroviral-Mediated Microglial Activation by Attenuating Autophagy-Lysosomal Dysfunction

  2020cites this paper
• Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis

  2020cites this paper
• The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

  2020cites this paper
• Differential Contribution of HIV-1 Subtypes B and C to Neurological Disorders: Mechanisms and Possible Treatments.

  2019cites this paper
• Intranasal insulin therapy reverses hippocampal dendritic injury and cognitive impairment in a model of HIV-associated neurocognitive disorders in EcoHIV-infected mice

  2019cites this paper
• Astrocyte activation and altered metabolism in normal aging, age-related CNS diseases, and HAND

  2019cites this paper
• Infections: Viruses

  2019cites this paper
• The Effects of Opioids on HIV Neuropathogenesis

  2019cites this paper
• Antiretroviral-Mediated Microglial Activation Involves Dysregulated Autophagy and Lysosomal Dysfunction

  2019cites this paper
• Microglia Mediate HIV-1 gp120-Induced Synaptic Degeneration in Spinal Pain Neural Circuits

  2019cites this paper
• Age-Related Decrease in Tyrosine Hydroxylase Immunoreactivity in the Substantia Nigra and Region-Specific Changes in Microglia Morphology in HIV-1 Tg Rats

  2019cites this paper
• Scaling Synapses in the Presence of HIV

  2018cites this paper
• Diet-Induced Obesity Elicits Macrophage Infiltration and Reduction in Spine Density in the Hypothalami of Male but Not Female Mice

  2018cites this paper
• HIV Tat causes synapse loss in a mouse model of HIV‐associated neurocognitive disorder that is independent of the classical complement cascade component C1q

  2018cites this paper