ArticleBrain, behavior, and immunity2020
Lipocalin-2 mediates HIV-1 induced neuronal injury and behavioral deficits by overriding CCR5-dependent protection.
Article in Brain, behavior, and immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- SHIV.D Infection Alters Production and Protein Composition of Myeloid-Derived Extracellular Vesicles.International journal of molecular sciences · 2026Article
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- Epigenetics and Mitochondrial Biogenesis: The Role of Sirtuins in HIV Neuropathogenesis.Molecular neurobiology · 2025Article
- EphB2-mediated ephrin-B reverse signaling on microglia drives an anti-viral, but inflammatory and neurotoxic response associated with HIV.Journal of neuroinflammation · 2025Article
- Article
- Interferon-β deficiency alters brain response to chronic HIV-1 envelope protein exposure in a transgenic model of NeuroHIV.Brain, behavior, and immunity · 2024Article
- A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury.Brain, behavior, and immunity · 2024Article
- Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.PNAS nexus · 2024Article
- Stress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice.Nature communications · 2024Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Systemic Inflammation Causes Microglial Dysfunction With a Vascular AD phenotype.Brain, behavior, & immunity - health · 2023Article
- Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus.Neurobiology of disease · 2022Article
- Article
- Review
- Chronic cerebral lipocalin 2 exposure elicits hippocampal neuronal dysfunction and cognitive impairment.Brain, behavior, and immunity · 2021Article
- Comprehensive review of lipocalin 2-mediated effects in lung inflammation.American journal of physiology. Lung cellular and molecular physiology · 2021Review
- Review
- Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.Brain, behavior, and immunity · 2021Article
- Transcriptomic and Genetic Profiling of HIV-Associated Neurocognitive Disorders.Frontiers in molecular biosciences · 2021Review
- A pivotal role for Interferon-α receptor-1 in neuronal injury induced by HIV-1.Journal of neuroinflammation · 2020Article
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
People living with HIV (PLWH) continue to develop HIV-associated neurocognitive disorders despite combination anti-retroviral therapy. Lipocalin-2 (LCN2) is an acute phase protein that has been implicated in neurodegeneration and is upregulated in a transgenic mouse model of HIV-associated brain injury. Here we show that LCN2 is significantly upregulated in neocortex of a subset of HIV-infected individuals with brain pathology and correlates with viral load in CSF and pro-viral DNA in neocortex. However, the question if LCN2 contributes to HIV-associated neurotoxicity or is part of a protective host response required further investigation. We found that the knockout of LCN2 in transgenic mice expressing HIVgp120 in the brain (HIVgp120tg) abrogates behavioral impairment, ameliorates neuronal damage, and reduces microglial activation in association with an increase of the neuroprotective CCR5 ligand CCL4. In vitro experiments show that LCN2 neurotoxicity also depends on microglia and p38 MAPK activity. Genetic ablation of CCR5 in LCN2-deficient HIVgp120tg mice restores neuropathology, suggesting that LCN2 overrides neuroprotection mediated by CCR5 and its chemokine ligands. RNA expression of 168 genes involved in neurotransmission reveals that neuronal injury and protection are each associated with genotype- and sex-specific patterns affecting common neural gene networks. In conclusion, our study identifies LCN2 as a novel factor in HIV-associated brain injury involving CCR5, p38 MAPK and microglia. Furthermore, the mechanistic interaction between LCN2 and CCR5 may serve as a diagnostic and therapeutic target in HIV patients at risk of developing brain pathology and neurocognitive impairment.
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