ArticleNeurobiology of disease2022
Neutral sphingomyelinase 2 inhibition attenuates extracellular vesicle release and improves neurobehavioral deficits in murine HIV.
Article in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The role of microRNAs in executive functions: a comprehensive review and bioinformatics analysis of human and animal studies.Molecular psychiatry · 2026Review
- Sex-specific gut mycobiome dysbiosis activates macrophage dectin-1 signaling to drive neurobehavioral deficits in EcoHIV-infected mice.Brain, behavior, and immunity · 2026Article
- EcoHIV Infection Disrupts Dopamine and Serotonin Transporter Function, Altering Release Dynamics in C57BL/6J Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Unveiling the role of extracellular vesicles in HIV infection: molecular mechanisms, viral persistence, and therapeutic opportunities.FEMS microbiology reviews · 2026Review
- Targeting NAAG metabolism restores cognition and synaptic integrity in EcoHIV-infected mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.bioRxiv : the preprint server for biology · 2025Article
- Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.Biomedicines · 2025Review
- Update on the roles and applications of extracellular vesicles in depression.World journal of psychiatry · 2025Review
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Metabolomics of Multiple Sclerosis Lesions Demonstrates Lipid Changes Linked to Alterations in Transcriptomics-Based Cellular Profiles.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis.Viruses · 2024Article
- Bridging brain and blood: a prospective view on neuroimaging-exosome correlations in HIV-associated neurocognitive disorders.Frontiers in neurology · 2024Review
- Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in an Alzheimer's disease mouse model.Translational neurodegeneration · 2023Article
- Neutral sphingomyelinase 2 inhibitors based on the pyrazolo[1,5-a]pyrimidin-3-amine scaffold.European journal of medicinal chemistry · 2023Article
- CCL2 is required for initiation but not persistence of HIV infection mediated neurocognitive disease in mice.Scientific reports · 2023Article
- RNA-Binding Proteins as Epigenetic Regulators of Brain Functions and Their Involvement in Neurodegeneration.International journal of molecular sciences · 2022Review
- Buprenorphine reverses neurocognitive impairment in EcoHIV infected mice: A potential therapy for HIV-NCI.Frontiers in immunology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
People living with HIV (PLH) have significantly higher rates of cognitive impairment (CI) and major depressive disorder (MDD) versus the general population. The enzyme neutral sphingomyelinase 2 (nSMase2) is involved in the biogenesis of ceramide and extracellular vesicles (EVs), both of which are dysregulated in PLH, CI, and MDD. Here we evaluated EcoHIV-infected mice for behavioral abnormalities relevant to depression and cognition deficits, and assessed the behavioral and biochemical effects of nSMase2 inhibition. Mice were infected with EcoHIV and daily treatment with either vehicle or the nSMase2 inhibitor (R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)-carbamate (PDDC) began 3 weeks post-infection. After 2 weeks of treatment, mice were subjected to behavior tests. EcoHIV-infected mice exhibited behavioral abnormalities relevant to MDD and CI that were reversed by PDDC treatment. EcoHIV infection significantly increased cortical brain nSMase2 activity, resulting in trend changes in sphingomyelin and ceramide levels that were normalized by PDDC treatment. EcoHIV-infected mice also exhibited increased levels of brain-derived EVs and altered microRNA cargo, including miR-183-5p, miR-200c-3p, miR-200b-3p, and miR-429-3p, known to be associated with MDD and CI; all were normalized by PDDC. In conclusion, inhibition of nSMase2 represents a possible new therapeutic strategy for the treatment of HIV-associated CI and MDD.
Indexed as
Identifiers
What OpenQuestion holds
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.