ArticleAntimicrobial agents and chemotherapy2016
Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Effects of HIV and azidothymidine on Alzheimer's-like pathology and amyloid beta transporters in hu-PBL-NSG mice, brain endothelial amyloid beta uptake and endothelial barrier integrity.Fluids and barriers of the CNS · 2026Article
- Investigation of CNS damage following HIV infection and methamphetamine exposure using human iPSC-derived microglia and 3D cerebral assembloid models.bioRxiv : the preprint server for biology · 2025Article
- Review
- Antiretroviral drugs from multiple classes induce loss of excitatory synapses between hippocampal neurons in culture.Frontiers in pharmacology · 2024Article
- Pathogenic mechanisms of human immunodeficiency virus (HIV)-associated pain.Molecular psychiatry · 2023Review
- Brain opportunistic infections and tumors in people living with HIV - still a challenge in efficient antiretroviral therapy era.Journal of neurovirology · 2023Observational
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- Methamphetamine augments HIV-1 gp120 inhibition of synaptic transmission and plasticity in rat hippocampal slices: Implications for methamphetamine exacerbation of HIV-associated neurocognitive disorders.Neurobiology of disease · 2022Article
- Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis.Annals of medicine · 2021Review
- Methamphetamine Enhances HIV-Induced Aberrant Proliferation of Neural Progenitor Cells via the FOXO3-Mediated Mechanism.Molecular neurobiology · 2021Article
- Advances in the Experimental Models of HIV-Associated Neurological Disorders.Current HIV/AIDS reports · 2021Review
- Integrated Systems Analysis of Mixed Neuroglial Cultures Proteome Post Oxycodone Exposure.International journal of molecular sciences · 2021Article
- TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use.Journal of neurovirology · 2021Article
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Review
- 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
- Transcriptomic and Genetic Profiling of HIV-Associated Neurocognitive Disorders.Frontiers in molecular biosciences · 2021Review
- An update on drug-drug interactions between antiretroviral therapies and drugs of abuse in HIV systems.Expert opinion on drug metabolism & toxicology · 2020Review
- Lipocalin-2 mediates HIV-1 induced neuronal injury and behavioral deficits by overriding CCR5-dependent protection.Brain, behavior, and immunity · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.
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