Evidence map›Paper›PMID 34278533›Full record

ArticleMolecular neurobiology2021

Activation of the Hippocampal LXRβ Improves Sleep-Deprived Cognitive Impairment by Inhibiting Neuroinflammation.

Chen Qiu, Min Wang, Wen Yu, Zheng Rong, He-Sheng Zheng, Ting Sun, Shui-Bing Liu, Ming-Gao Zhao, Yu-Mei Wu

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Microglial Feimin Alleviates Cognitive Impairment in High-Fat Diet-Fed Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
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  5. Review
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  9. Article
  10. Microglia and Sleep Disorders.Advances in neurobiology · 2024
    Review
  11. Article
  12. Article
  13. Review
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  15. 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

9 authors at 2 institutions in 1 country.

Chen Qiu *Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Min Wang *Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Wen YuDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Zheng RongDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
He-Sheng ZhengDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Ting SunDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Shui-Bing LiuDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Ming-Gao ZhaoDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032.
Yu-Mei WuDepartment of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China, 710032. yumeiwu@fmmu.edu.cn.ORCID http://orcid.org/0000-0002-8524-1254
Air Force Medical University · CNShaanxi University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sleep deprivation (SD) leads to cognitive impairment due to neuroinflammation associated with impaired hippocampal neuronal plasticity and memory processes. Liver X receptors (LXRs), including LXRα and LXRβ isoforms, are crucial for synaptic plasticity and neuroinflammation. However, the potential roles of LXRs in the pathogenesis of cognitive impairment induced by SD remain unclear. We revealed that SD resulted in LXRβ reduction in the hippocampus, which was associated with upregulated expression of high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB p65, and knockdown of hippocampal LXRβ by shRNA (shLXRβ) led to cognitive impairment. GW3965, a dual agonist for both LXRα and LXRβ, ameliorated SD-induced cognitive impairment by inhibiting microglia activation, suppressing HMGB1/TLR4/NF-κB p65 pathway, and ultimately affecting the hippocampal expression of inflammatory cytokines in SD mice. LXRβ knockdown by shLXRβ abrogated the GW3965-mediated inhibition of the HMGB1/TLR4/NF-κB p65 pathway, therefore, abolishing the cognitive improvement. Moreover, inhibition of HMGB1 by glycyrrhizin (GLY) synergistic promoted GW3965-mediated anti-inflammation in activated microglia after lipopolysaccharide (LPS)/ATP stimulation and facilitated the cognitive improvement after GW administration by activating LXRβ. All the data suggested that GW3965 ameliorated impaired cognition in SD mice by suppressing the HMGB1/TLR4/NF-κB p65 pathway followed LXRβ activation. This study correlates a deficit of LXRβ in cognitive dysfunction in SD associated with HMGB1 inflammatory pathway in hippocampus, and LXRs may serve as a potential therapeutic target for cognitive impairment with anti-inflammation.

Indexed as

AnimalsAnti-Inflammatory AgentsBenzoatesBenzylaminesCognitive DysfunctionDose-Response Relationship, DrugGlycyrrhizic AcidHippocampusLiver X ReceptorsMaleMiceMice, Inbred C57BLMicroinjectionsNeuroinflammatory DiseasesRandom AllocationSleep DeprivationAnti-Inflammatory AgentsBenzoatesBenzylaminesGlycyrrhizic AcidGW 3965Liver X ReceptorsCognitive impairmentHigh mobility group box 1 (HMGB1)Liver X receptorsMicrogliaNeuroinflammationSleep deprivation

Identifiers

PMID34278533
OpenAlexW3179268784

What OpenQuestion holds

Textmetadata
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.