Evidence map›Paper›PMID 21291924›Full record

ArticleNeuroscience research2011

Parallel high throughput neuronal toxicity assays demonstrate uncoupling between loss of mitochondrial membrane potential and neuronal damage in a model of HIV-induced neurodegeneration.

Michael G White, Ying Wang, Cagla Akay, Kathryn A Lindl, Dennis L Kolson, Kelly L Jordan-Sciutto

Abstract read
In one paragraph

Article in Neuroscience research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Dolutegravir induces endoplasmic reticulum stress at the blood-brain barrier.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  16. Independent effects of HIV, aging, and HAART on brain volumetric measures.Journal of acquired immune deficiency syndromes (1999) · 2012
    Article
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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

6 authors at 1 institution in 1 country.

Michael G WhiteDepartment of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ying Wang
Cagla Akay
Kathryn A Lindl
Dennis L Kolson
Kelly L Jordan-Sciutto
University of Pennsylvania · US

Funding

TRAINING IN HIV PATHOGENESIST32AI007632 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Frederic D Bushman, James L. Riley · 2000 to 2026
$10.6M
SCID HU MODEL FOR HIV INFECTION OF THE CNSP01NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 1989 to 2007
$8.2M
ROLE OF CELL CYCLE PROTEINS IN HIV ENCEPHALITISR01NS041202 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JORDAN-SCIUTTO, KELLY L · 2001 to 2015
$4.5M
HIV Neural Apoptosis:Mechanisms, Pathways &ProtectionR01NS043994 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI KOLSON, DENNIS LARRY · 2003 to 2011
$3.5M
Molecular and Cellular Biology of HIV EncephalopathyP50NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 2008 to 2009
$2.2M
Effects of the Integrated Stress Response in HIV Associated DementiaR01NS056885 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI JORDAN-SCIUTTO, KELLY L · 2007 to 2011
$2.0M
NIAID NIH HHS T32 AI007632NIAID NIH HHS T32 AI07632NINDS NIH HHS NS043994NINDS NIH HHS NS056885NINDS NIH HHS NS27405NINDS NIH HHS NS41202NINDS NIH HHS P01 NS027405NINDS NIH HHS R01 NS041202NINDS NIH HHS R01 NS043994NINDS NIH HHS R01 NS056885
6 · The paper itself

Abstract

Neurocognitive deficits seen in HIV-associated neurocognitive disorders (HANDs) are attributed to the release of soluble factors from CNS-resident, HIV-infected and/or activated macrophages and microglia. To study HIV-associated neurotoxicity, we used our in vitro model in which primary rat neuronal/glial cultures are treated with supernatants from cultured human monocyte-derived macrophages, infected with a CNS-isolated HIV-1 strain (HIV-MDM). We found that neuronal damage, detected as a loss of microtubule-associated protein-2 (MAP2), begins as early as 2h and is preceded by a loss of mitochondrial membrane potential (Δψ(m)). Interestingly, inhibitors of calpains, but not inhibitors of caspases, blocked MAP2 loss, however neither type of inhibitor prevented the loss of Δψ(m). To facilitate throughput for these studies, we refined a MAP2 cell-based-ELISA whose data closely compare with our standardized method of hand counting neurons. In addition, we developed a tetramethyl rhodamine methyl ester (TMRM)-based multi-well fluorescent plate assay for the evaluation of whole culture Δψ(m). Together, these findings indicate that calpain activation and loss of Δψ(m) may be parallel pathways to death in HIV-MDM-treated neurons and also demonstrate the validity of plate assays for assessing multiple experimental parameters as is useful for screening neurotherapeutics for neuronal damage and death.

Indexed as

AIDS Dementia ComplexAnimalsCalpainCell Culture TechniquesCell DeathCells, CulturedMacrophagesMembrane Potential, MitochondrialMicrotubule-Associated ProteinsMitochondrial DiseasesNerve DegenerationNeuronsRatsRats, Sprague-DawleyRhodaminesCalpainMicrotubule-Associated ProteinsRhodaminestetramethylrhodamine methyl ester

Identifiers

PMID21291924
PMCPMC3091994
OpenAlexW2049147024

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.