ArticlePloS one2014
Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.
Article in PloS one, 2014. 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, 47 citations in OpenAlex.
- Association of nucleos(t)ide analogue therapy with Parkinson disease in chronic hepatitis B patients.Scientific reports · 2025Article
- Impact of nucleos(t)ide analogue therapy on the incidence of Alzheimer's disease in patients with chronic hepatitis B virus infection.Alzheimer's research & therapy · 2025Article
- Persistent low-Level viremia in persons living with HIV undertreatment: An unresolved status.Virulence · 2021Review
- Mitochondrial DNA Damage and Brain Aging in Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Mitochondrial DNA Instability Is Common in HIV-Exposed Uninfected Newborns.Journal of clinical medicine · 2021Article
- Effects of combination antiretroviral drugs (cART) on hippocampal neuroplasticity in female mice.Journal of neurovirology · 2021Article
- CNS Neurotoxicity of Antiretrovirals.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Cerebral Vascular Toxicity of Antiretroviral Therapy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Associations between Antiretrovirals and Cognitive Function in Women with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- 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
- Efficacy and Safety of Switching to Dolutegravir With Boosted Darunavir in Virologically Suppressed Adults With HIV-1: A Randomized, Open-Label, Multicenter, Phase 3, Noninferiority Trial: The DUALIS Study.Open forum infectious diseases · 2020Article
- Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.Frontiers in genetics · 2020Article
- Depletion of Mitochondrial DNA in Differentiated Retinal Pigment Epithelial Cells.Scientific reports · 2019Article
- HIV infection and latency induce a unique metabolic signature in human macrophages.Scientific reports · 2019Article
- BrainJournal of neuroinflammation · 2018Article
- DRAM Is Involved in Regulating Nucleoside Analog-Induced Neuronal Autophagy in a p53-Independent Manner.Molecular neurobiology · 2018Article
- Neuronal Stress and Injury Caused by HIV-1, cART and Drug Abuse: Converging Contributions to HAND.Brain sciences · 2017Review
- Interventions for Neurocognitive Dysfunction.Current HIV/AIDS reports · 2017Review
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Neurotoxicity in the Post-HAART Era: Caution for the Antiretroviral Therapeutics.Neurotoxicity research · 2016Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleoside analogue reverse transcriptase inhibitor (NRTI), an integral component of highly active antiretroviral therapy (HAART), was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier (BBB) and the complex microenvironment of the central nervous system (CNS). In this study, the Balb/c mice were administered 50 mg/kg stavudine (D4T), 100 mg/kg zidovudine (AZT), 50 mg/kg lamivudine (3TC) or 50 mg/kg didanosine (DDI) per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA (mtDNA) levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver (except for 3TC) and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.
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