ArticleMolecular and cellular neurosciences2013
Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures.
Article in Molecular and cellular neurosciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND.Current HIV/AIDS reports · 2026Review
- HIV-1 Tat expression drives progressive synaptic decline: evidence from longitudinal [NeuroImmune pharmacology and therapeutics · 2026Article
- EcoHIV Infection Disrupts Dopamine and Serotonin Transporter Function, Altering Release Dynamics in C57BL/6J Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Neurological, Behavioral, and Pathophysiological Characterization of the Co-Occurrence of Substance Use and HIV: A Narrative Review.Brain sciences · 2023Review
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence.International journal of molecular sciences · 2023Article
- Astrocytes: Role in pathogenesis and effect of commonly misused drugs in the HIV infected brain.Current research in neurobiology · 2023Review
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- HIV-1 Tat reduces apical dendritic spine density throughout the trisynaptic pathway in the hippocampus of male transgenic mice.Neuroscience letters · 2022Article
- Clathrin-nanoparticles deliver BDNF to hippocampus and enhance neurogenesis, synaptogenesis and cognition in HIV/neuroAIDS mouse model.Communications biology · 2022Article
- Morphological Changes of Frontal Areas in Male Individuals With HIV: A Deformation-Based Morphometry Analysis.Frontiers in neurology · 2022Article
- Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection.Microorganisms · 2021Review
- Effects of combination antiretroviral drugs (cART) on hippocampal neuroplasticity in female mice.Journal of neurovirology · 2021Article
- Monoacylglycerol Lipase Inhibitor MJN110 Reduces Neuronal Hyperexcitability, Restores Dendritic Arborization Complexity, and Regulates Reward-Related Behavior in Presence of HIV-1 Tat.Frontiers in neurology · 2021Article
- Functional impact of HIV-1 Tat on cells of the CNS and its role in HAND.Cellular and molecular life sciences : CMLS · 2020Review
- Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies.Open biology · 2020Review
- Modeling HIV-1 neuropathogenesis using three-dimensional human brain organoids (hBORGs) with HIV-1 infected microglia.Scientific reports · 2020Article
- Conditional expression of HIV-1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex-dependent manner.European journal of pain (London, England) · 2020Article
- Cross-talk between microglia and neurons regulates HIV latency.PLoS pathogens · 2019Article
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2 authors.
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Abstract
Human immunodeficiency virus (HIV) infection of the CNS produces dendritic damage that correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). HIV-induced neurotoxicity results in part from viral proteins shed from infected cells, including the HIV transactivator of transcription (Tat). We previously showed that Tat binds to the low density lipoprotein receptor-related protein (LRP), resulting in overactivation of NMDA receptors, activation of the ubiquitin-proteasome pathway, and subsequent loss of postsynaptic densities. Here, we show that Tat also induces a loss of presynaptic terminals. The number of presynaptic terminals was quantified using confocal imaging of synaptophysin fused to green fluorescent protein (Syn-GFP). Tat-induced loss of presynaptic terminals was secondary to excitatory postsynaptic mechanisms because treatment with an LRP antagonist or an NMDA receptor antagonist inhibited this loss. Treatment with nutlin-3, an E3 ligase inhibitor, prevented Tat-induced loss of presynaptic terminals. These data suggest that Tat-induced loss of presynaptic terminals is a consequence of excitotoxic postsynaptic activity. We previously found that ifenprodil, an NR2B subunit-selective NMDA receptor antagonist, induced recovery of postsynaptic densities. Here we show that Tat-induced loss of presynaptic terminals was reversed by ifenprodil treatment. Thus, Tat-induced loss of presynaptic terminals is reversible, and this recovery can be initiated by inhibiting a subset of postsynaptic NMDA receptors. Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients.
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