Evidence map›Paper›PMID 30325063›Full record

ArticleGlia2018

HIV Tat causes synapse loss in a mouse model of HIV-associated neurocognitive disorder that is independent of the classical complement cascade component C1q.

Jennetta W Hammond, Wen Q Qiu, Daniel F Marker, Jeffrey M Chamberlain, Will Greaves-Tunnell, Matthew J Bellizzi, Shao-Ming Lu, Harris A Gelbard

Abstract read
In one paragraph

Article in Glia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 30% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Infectious Diseases.Advances in neurobiology · 2024
    Review
  6. C1q is elevated during chronicFrontiers in immunology · 2024
    Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Jennetta W HammondCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.ORCID 0000-0002-3949-1594
Wen Q QiuCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Daniel F MarkerCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Jeffrey M ChamberlainCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Will Greaves-TunnellCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Matthew J BellizziCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Shao-Ming LuCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
Harris A GelbardCenter for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.
University of Rochester Medical Center · US

Funding

Targeted Neuro Protection of HIV-1 Associated Neurologic DiseaseP01MH064570 · NIMH · UNIVERSITY OF ROCHESTER · PI GELBARD, HARRIS A · 2001 to 2014
$19.4M
Virology/Immunology CoreP30AI078498 · NIAID · UNIVERSITY OF ROCHESTER · PI DEWHURST, STEPHEN · 2008 to 2018
$14.6M
Novel Kinase and Nanoformulated Protease Inhibitors for Eradication of CNS HIV-1R01MH104147 · NIMH · UNIVERSITY OF ROCHESTER · PI GELBARD, HARRIS A · 2014 to 2018
$3.2M
PAF: Presynaptic and Postsynaptic Mechanisms of Injury in HANDF32MH105288 · NIMH · UNIVERSITY OF ROCHESTER · PI HAMMOND, JENNETTA W · 2014 to 2016
$166k
National Institute of Allergy and Infectious Diseases P30 AI078498NIAID NIH HHS P30 AI078498NIMH NIH HHS F32 MH105288NIMH NIH HHS P01 MH064570NIMH NIH HHS R01 MH104147
6 · The paper itself

Abstract

Microglial activation, increased proinflammatory cytokine production, and a reduction in synaptic density are key pathological features associated with HIV-associated neurocognitive disorders (HAND). Even with combination antiretroviral therapy (cART), more than 50% of HIV-positive individuals experience some type of cognitive impairment. Although viral replication is inhibited by cART, HIV proteins such as Tat are still produced within the nervous system that are neurotoxic, involved in synapse elimination, and provoke enduring neuroinflammation. As complement deposition on synapses followed by microglial engulfment has been shown during normal development and disease to be a mechanism for pruning synapses, we have tested whether complement is required for the loss of synapses that occurs after a cortical Tat injection mouse model of HAND. In Tat-injected animals evaluated 7 or 28 days after injection, levels of early complement pathway components, C1q and C3, are significantly elevated and associated with microgliosis and a loss of synapses. However, C1qa knockout mice have the same level of Tat-induced synapse loss as wild-type (WT) mice, showing that the C1q-initiated classical complement cascade is not driving synapse removal during HIV1 Tat-induced neuroinflammation.

Indexed as

AnimalsBone MarrowBone Marrow TransplantationCalcium-Binding ProteinsCerebral CortexCognitive DysfunctionComplement C1qComplement C3Disease Models, AnimalGene Expression RegulationGliosisHIV InfectionsMaleMiceMice, Inbred C57BLMice, TransgenicAif1 protein, mouseC3 protein, mouseCalcium-Binding ProteinsComplement C1qComplement C3Microfilament ProteinsNerve Tissue ProteinsReceptors, Interleukin-8Atat Gene Products, Human Immunodeficiency VirusC1qcomplementHIVsynapseTat

Identifiers

PMID30325063
PMCPMC6309507
OpenAlexW2897281558

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.