Evidence map›Paper›PMID 35123512›Full record

ArticleJournal of neuroinflammation2022

Long-term running exercise improves cognitive function and promotes microglial glucose metabolism and morphological plasticity in the hippocampus of APP/PS1 mice.

Shan-Shan Zhang, Lin Zhu, Yan Peng, Lei Zhang, Feng-Lei Chao, Lin Jiang, Qian Xiao, Xin Liang, Jing Tang, Hao Yang and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 3 pooled it
10.7field-weighted citation impact, top 1% 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

72 citing papers in PubMed, 3 syntheses or guidelines pooled it, 134 citations in OpenAlex.

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12 more citing papers are in PubMed but not listed here.

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

14 authors at 1 institution in 1 country.

Shan-Shan ZhangDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Lin ZhuDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Yan PengDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Lei ZhangDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Feng-Lei ChaoDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Lin JiangExperimental Teaching Management Center, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Qian XiaoDepartment of Radioactive Medicine, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Xin LiangDepartment of Pathophysiology, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Jing TangDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Hao YangDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Qi HeDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Yi-Jing GuoDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Chun-Ni ZhouDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China. 602568297@qq.com.
Yong TangDepartment of Histology and Embryology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, People's Republic of China. ytang062@163.com.ORCID http://orcid.org/0000-0001-8449-5546
Chongqing Medical University · CN

Funding

National Natural Science Foundation of China 81671259National Natural Science Foundation of China 81801269National Natural Science Foundation of China 81871073Natural Science Foundation of Chongqing cstc2020jcyj-msxmX0125Natural Science Foundation of Chongqing cstc2020jcyj-msxmX0354
6 · The paper itself

Abstract

backgroundThe role of physical exercise in the prevention of Alzheimer's disease (AD) has been widely studied. Microglia play an important role in AD. Triggering receptor expressed in myeloid cells 2 (TREM2) is expressed on microglia and is known to mediate microglial metabolic activity and brain glucose metabolism. However, the relationship between brain glucose metabolism and microglial metabolic activity during running exercise in APP/PS1 mice remains unclear.

methodsTen-month-old male APP/PS1 mice and wild-type mice were randomly divided into sedentary groups or running groups (AD_Sed, WT_Sed, AD_Run and WT_Run, n = 20/group). Running mice had free access to a running wheel for 3 months. Behavioral tests, [18]F-FDG-PET and hippocampal RNA-Seq were performed. The expression levels of microglial glucose transporter (GLUT5), TREM2, soluble TREM2 (sTREM2), TYRO protein tyrosine kinase binding protein (TYROBP), secreted phosphoprotein 1 (SPP1), and phosphorylated spleen tyrosine kinase (p-SYK) were estimated by western blot or ELISA. Immunohistochemistry, stereological methods and immunofluorescence were used to investigate the morphology, proliferation and activity of microglia.

resultsLong-term voluntary running significantly improved cognitive function in APP/PS1 mice. Although there were few differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) showed enriched glycometabolic pathways in APP/PS1 running mice. Running exercise increased FDG uptake in the hippocampus of APP/PS1 mice, as well as the protein expression of GLUT5, TREM2, SPP1 and p-SYK. The level of sTREM2 decreased in the plasma of APP/PS1 running mice. The number of microglia, the length and endpoints of microglial processes, and the ratio of GLUT5

conclusionsRunning exercise inhibited TREM2 shedding and maintained TREM2 protein levels, which were accompanied by the promotion of brain glucose metabolism, microglial glucose metabolism and morphological plasticity in the hippocampus of AD mice. Microglia might be a structural target responsible for the benefits of running exercise in AD. Promoting microglial glucose metabolism and morphological plasticity modulated by TREM2 might be a novel strategy for AD treatment.

Indexed as

Alzheimer DiseaseMicrogliaAmyloid beta-Protein PrecursorAnimalsCognitionDisease Models, AnimalGlucoseHippocampusMaleMembrane GlycoproteinsMiceMice, TransgenicPresenilin-1Receptors, ImmunologicAmyloid beta-Protein PrecursorGlucoseMembrane GlycoproteinsPresenilin-1Receptors, ImmunologicTrem2 protein, mouseAlzheimer’s diseaseHippocampusMicrogliaRunning exerciseTREM2

Identifiers

PMID35123512
PMCPMC8817568
OpenAlexW4213358325

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LicenceCC BY
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Registered trials

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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.