Evidence map›Paper›PMID 29197398›Full record

ArticleJournal of neuroinflammation2017

Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress.

Dan Zhao, Xulin Xu, Linna Pan, Wei Zhu, Xiaopei Fu, Lianjun Guo, Qing Lu, Jian Wang

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026
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  9. An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Dan ZhaoDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xulin XuDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Linna PanDepartment of Neurology, The Second Hospital of Nanchang, Nanchang, 330003, China.
Wei ZhuDepartment of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Xiaopei FuDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Lianjun GuoDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Qing LuDepartment of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. qinglu@mail.hust.edu.cn.
Jian WangDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, 21205, USA.
Huazhong University of Science and Technology · CNJohns Hopkins Medicine · USSecond Hospital of Nanchang · CN

Funding

Neuroprotective effect of flavanol (-) epicatechin after intracerebral hemorrhageR01AT007317 · NCCIH · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$2.0M
PGE2 EP1 and EP3 receptors as therapeutic targets in intracerebral hemorrhageR01NS078026 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2012 to 2016
$1.8M
Microglia/macrophage polarization after intracerebral hemorrhageR56NS096549 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2017 to 2017
$488k
Depression after Intracerebral Hemorrhage: Role of Nrf2R21NS101614 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WANG, JIAN · 2017 to 2018
$450k
Foundation for the National Institutes of Health R01AT007317Foundation for the National Institutes of Health R21 NS101614Foundation for the National Institutes of Health R56 NS096549NCCIH NIH HHS R01 AT007317NINDS NIH HHS R01 NS078026NINDS NIH HHS R21 NS101614NINDS NIH HHS R56 NS096549the National Natural Science Foundation of China 5351603910the National Natural Science Foundation of China 81001432
6 · The paper itself

Abstract

backgroundIt has been shown that chronic stress-induced depression is associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic acetylcholine receptors (α7nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and α7nAChR in chronic stress has not yet been examined.

methodsIn this study, we used a well-documented model of depression in which mice were exposed to 6 h of restraint stress for 21 consecutive days. Components of cholinergic signaling and TLR4 signaling were analyzed in the hippocampus. The main targets of neuroinflammation and neuronal damage were also evaluated after a series of tests for depression-like behavior.

resultsChronic restraint stress (CRS) induced alterations in components of central cholinergic signaling in hippocampus, including increases in choline acetyltransferase protein expression and decreases in nuclear STAT3 signaling. CRS also increased TLR4 signaling activity, interleukin-1β, and tumor necrosis factor-α expression, microglial activation, and neuronal morphologic changes. Cholinergic stimulation with the α7nAChR agonist DMXBA significantly alleviated CRS-induced depressive-like behavior, neuroinflammation, and neuronal damage, but these effects were abolished by the selective α7nAChR antagonist α-bungarotoxin. Furthermore, activation of α7nAChRs restored the central cholinergic signaling function, inhibited TLR4-mediated inflammatory signaling and microglial activity, and increased the number of regulatory T cells in the hippocampus.

conclusionsThese findings provide evidence that α7nAChR activation mitigates CRS-induced neuroinflammation and cell death, suggesting that α7nAChRs could be a new therapeutic target for the prevention and treatment of depression.

Indexed as

alpha7 Nicotinic Acetylcholine ReceptorAnimalsDepressionDisease Models, AnimalHippocampusMaleMiceRestraint, PhysicalStress, Psychologicalalpha7 Nicotinic Acetylcholine ReceptorChronic restraint stressDepressionNeuroinflammationNicotinic acetylcholine receptorTLR4

Identifiers

PMID29197398
PMCPMC5712092
OpenAlexW2773319991

What OpenQuestion holds

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LicenceCC BY
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.