ArticleScientific reports2019
Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Article
- HIV-associated sensory neuropathy: current progress and future challenges.NeuroImmune pharmacology and therapeutics · 2025Review
- Caloric restriction mimetic 2-deoxyglucose alters metabolic and transcriptomic phenotype in association with changes in chromatin accessibility in human astrocytes.Scientific reports · 2025Article
- Evaluation of Hippocampal Microanatomy and Neuro-Biomarkers Following Administration of Silver Nanoparticles Conjugated with Tenofovir Disoproxil Fumarate in Experimental Diabetic Rats.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Alzheimer-Type Cerebral Amyloidosis in the Context of HIV Infection: Implications for a Proposed New Treatment Approach.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Sera from people with HIV and depression induce commensurate metabolic alterations in astrocytes: toward precision diagnoses and therapies.NeuroImmune pharmacology and therapeutics · 2024Article
- Mitochondrial DNA and Electron Transport Chain Protein Levels Are Altered in Peripheral Nerve Tissues from Donors with HIV Sensory Neuropathy: A Pilot Study.International journal of molecular sciences · 2024Article
- Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Tenofovir disoproxil fumarate mediates neuronal injury by inducing neurotoxicity.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Article
- Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.Journal of neurovirology · 2023Article
- GP120 and tenofovir alafenamide alter cannabinoid receptor 1 expression in hippocampus of mice.Journal of neurovirology · 2023Article
- Persistent sensory changes and sex differences in transgenic mice conditionally expressing HIV-1 Tat regulatory protein.Experimental neurology · 2022Article
- The Potential ofCells · 2022Review
- Neuropathic pain correlates with worsening cognition in people with human immunodeficiency virus.Brain : a journal of neurology · 2022Observational
- Review
- Frontal lobe microglia, neurodegenerative protein accumulation, and cognitive function in people with HIV.Acta neuropathologica communications · 2022Article
- Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases.Brain sciences · 2022Article
- Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.Journal of neuroendocrinology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Mounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain.
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Registered trials
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