ArticleAIDS (London, England)2016
HIV protease inhibitors disrupt astrocytic glutamate transporter function and neurobehavioral performance.
Article in AIDS (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial.Trials · 2016Trial
- The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View.Journal of clinical medicine · 2024Review
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- The Impact of COVID-19 and Vaccine on the Human Nervous System.Neuroendocrinology · 2022Review
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- CNS Neurotoxicity of Antiretrovirals.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- The far-reaching HAND of cART: cART effects on astrocytes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- A review of the potential mechanisms of neuronal toxicity associated with antiretroviral drugs.Journal of neurovirology · 2020Review
- The broad-spectrum antiviral recommendations for drug discovery against COVID-19.Drug metabolism reviews · 2020Review
- Article
- The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside.Neuropsychiatric disease and treatment · 2020Review
- Triumeq Increases Excitability of Pyramidal Neurons in the Medial Prefrontal Cortex by Facilitating Voltage-Gated CaFrontiers in pharmacology · 2020Article
- The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs.Frontiers in cellular and infection microbiology · 2020Review
- The impact of substance abuse on HIV-mediated neuropathogenesis in the current ART era.Brain research · 2019Review
- New Molecular Insights into the Inhibition of Dipeptidyl Peptidase-4 by Natural Cyclic Peptide Oxytocin.Molecules (Basel, Switzerland) · 2019Article
- The Effects of Opioids on HIV Neuropathogenesis.Frontiers in immunology · 2019Review
- Association of antiretroviral therapy with brain aging changes among HIV-infected adults.AIDS (London, England) · 2018Article
- Quercetin attenuates AZT-induced neuroinflammation in the CNS.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
Abstract
objectiveThe neurotoxic actions of the HIV protease inhibitors, amprenavir (APV) and lopinavir (LPV) were investigated.
designWith combination antiretroviral therapy (cART), HIV-infected persons exhibit neurocognitive impairments, raising the possibility that cART might exert adverse central nervous system (CNS) effects. We examined the effects of LPV and APV using in-vitro and in-vivo assays of CNS function.
methodsGene expression, cell viability and amino-acid levels were measured in human astrocytes, following exposure to APV or LPV. Neurobehavioral performance, amino-acid levels and neuropathology were examined in HIV-1 Vpr transgenic mice after treatment with APV or LPV.
resultsExcitatory amino-acid transporter-2 (EAAT2) expression was reduced in astrocytes treated with LPV or APV, especially LPV (P < 0.05), which was accompanied by reduced intracellular L-glutamate levels in LPV-treated cells (P < 0.05). Treatment of astrocytes with APV or LPV reduced the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 (P < 0.05) although cell survival was unaffected. Exposure of LPV to astrocytes augmented glutamate-evoked transient rises in [Cai] (P < 0.05). Vpr mice treated with LPV showed lower concentrations of L-glutamate, L-aspartate and L-serine in cortex compared with vehicle-treated mice (P < 0.05). Total errors in T-maze assessment were increased in LPV and APV-treated animals (P < 0.05). EAAT2 expression was reduced in the brains of protease inhibitor-treated animals, which was associated with gliosis (P < 0.05).
conclusionThese results indicated that contemporary protease inhibitors disrupt astrocyte functions at therapeutic concentrations with enhanced sensitivity to glutamate, which can lead to neurobehavioral impairments. ART neurotoxicity should be considered in future therapeutic regimens for HIV/AIDS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.