Evidence map›Paper›PMID 34196664›Full record

ArticleBrain : a journal of neurology2021

Activation of α7 nicotinic acetylcholine receptor ameliorates HIV-associated neurology and neuropathology.

Xiaojie Zhao, Kelly Wilson, Victor Uteshev, Johnny J He

Open access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  5. Alzheimer's disease protective allele ofmedRxiv : the preprint server for health sciences · 2024
    Article
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  7. Review
  8. Long COVID as a Tauopathy: Of "Brain Fog" and "Fusogen Storms".International journal of molecular sciences · 2023
    Review
  9. 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

4 authors at 2 institutions in 1 country.

Xiaojie ZhaoDepartment of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA.ORCID 0000-0002-8080-0280
Kelly WilsonDepartment of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA.ORCID 0000-0002-4257-6302
Victor UteshevDepartment of Pharmacology and Neuroscience, Graduate School of Biomedical Sciences of University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Johnny J HeDepartment of Microbiology and Immunology, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA.
Rosalind Franklin University of Medicine and Science · USUniversity of North Texas · US

Funding

HIV Infection and Latency In AstrocytesR01DA043162 · NIDA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI HE, JOHNNY J · 2016 to 2020
$2.8M
miR-132, a new player in HIV/neuroAIDSR01NS094108 · NINDS · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI HE, JOHNNY J · 2015 to 2019
$2.7M
NIDA NIH HHS R01 DA043162NINDS NIH HHS R01 NS094108US National Institutes of Health R01DA043162
6 · The paper itself

Abstract

HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy are primarily manifested as impaired behaviours, glial activation/neuroinflammation and compromised neuronal integrity, for which there are no effective treatments currently available. In the current study, we used doxycycline-inducible astrocyte-specific HIV Tat transgenic mice (iTat), a surrogate HAND model, and determined effects of PNU-125096, a positive allosteric modulator of α7 nicotinic acetylcholine receptor (α7 nAChR) on Tat-induced behavioural impairments and neuropathologies. We showed that PNU-125096 treatment significantly improved locomotor, learning and memory deficits of iTat mice while inhibited glial activation and increased PSD-95 expression in the cortex and hippocampus of iTat mice. Using α7 nAChR knockout mice, we showed that α7 nAChR knockout eliminated the protective effects of PNU-125096 on iTat mice. In addition, we showed that inhibition of p38 phosphorylation by SB239063, a p38 MAPK-specific inhibitor exacerbated Tat neurotoxicity in iTat mice. Last, we used primary mouse cortical individual cultures and neuron-astrocytes co-cultures and in vivo staining of iTat mouse brain tissues and showed that glial activation was directly involved in the interplay among Tat neurotoxicity, α7 nAChR activation and the p38 MAPK signalling pathway. Taken together, these findings demonstrated for the first time that α7 nAChR activation led to protection against HAND and suggested that α7 nAChR modulator PNU-125096 holds significant promise for development of therapeutics for HAND.

Indexed as

AIDS Dementia Complexalpha7 Nicotinic Acetylcholine ReceptorAnimalsMiceMice, Inbred C57BLMice, Transgenictat Gene Products, Human Immunodeficiency Virusalpha7 Nicotinic Acetylcholine Receptortat Gene Products, Human Immunodeficiency VirusHANDHIV Tatp38 MAPKPAMα7 nAChR

Identifiers

PMID34196664
PMCPMC8677536
OpenAlexW3177394462

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.